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39712013 | 100 | Modular (universal) CAR-T platforms | Modular (universal) CAR T-platforms were developed to combat the limitations of traditional CAR-T therapy, allowing for multiple targeting of tumor-associated antigens and the ability to control CAR-T cell activity. The modular CAR-T platform consists of a universal receptor (signaling module) that recognizes an adapter molecule on the soluble module, which is responsible for antigen recognition. Multiple platforms have been developed over the last 12 years, and some of them have entered the clinical trial phase. This systematic review seeks to evaluate the different parameters of modular CAR-T platforms performance in animal models.
A systematic search of literature in the PubMed database and in Google Scholar and BASE (Bielefeld Academic Search Engine) search engines was performed according to predefined eligibility criteria. All studies conducted on xenograft mouse models with any variant of modular CAR-T platforms were included. Forest plots were generated for visual presentation of the extracted quantitative findings (standardized mean difference (SMD) and median survival rate (MSR)).
A total of 33 studies employing 15 different modular CAR-T platforms were included. The platforms varied in terms of CAR-T cells, soluble module doses, and their frequency of administration. The studies showed a reduction in tumor burden and in tumor volume compared to the combined negative group. In comparison with the positive control group, there was no significant change in tumor burden or volume. In all the included studies the experimental group had a higher survival probability compared to the combined negative group at the study endpoint, with no significant difference in survival rate compared to the positive control group.
The modular CAR-T platforms are generally effective and are a valuable addition to the arsenal of CAR therapy.
https://www.crd.york.ac.uk/prospero/ PROSPERO, identifier CRD42023443984. | [
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10.1136/jitc-2022-005934 | [
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"Yurina",
"Simonyan",
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"Bogolyubova"
] | [
"National Medical Research Center for Hematology, Moscow, Russia.",
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"National Medical Research Center for Hematology, Moscow, Russia.",
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39711794 | 101 | Armoring chimeric antigen receptor (CAR) T cells as micropharmacies for cancer therapy. | Chimeric antigen receptor (CAR)-T-cell therapy has emerged as a powerful weapon in the fight against cancer. However, its efficacy is often hindered by challenges such as limited tumor penetration, antigen escape, and immune suppression within the tumor microenvironment. This review explores the potential of armored CAR-T cells, or 'micropharmacies', in overcoming these obstacles and enhancing the therapeutic outcomes of adoptive T-cell (ATC) therapy. We delve into the engineering strategies behind these advanced therapies and the mechanisms through which they improve CAR-T-cell efficacy. Additionally, we discuss the latest advancements and research findings in the field, providing a comprehensive understanding of the role of armored CAR-T cells in cancer treatment. Ultimately, this review highlights the promising future of integrating micropharmacies into ATC therapy, paving the way for more effective and targeted cancer treatments. | [
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] | [
"BiTEs",
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"TRUCKs",
"immuno-oncology",
"micropharmacies",
"next-generation CARs"
] | 0 | 10.1016/j.iotech.2024.100739 | [
"Carcopino",
"Erdogan",
"Henrich",
"Kobold"
] | [
"Division of Clinical Pharmacology, Department of Medicine IV, University Hospital, Ludwig Maximilian University (LMU) of Munich, Munich, Germany.",
"Division of Clinical Pharmacology, Department of Medicine IV, University Hospital, Ludwig Maximilian University (LMU) of Munich, Munich, Germany.",
"Division of Clinical Pharmacology, Department of Medicine IV, University Hospital, Ludwig Maximilian University (LMU) of Munich, Munich, Germany.",
"Division of Clinical Pharmacology, Department of Medicine IV, University Hospital, Ludwig Maximilian University (LMU) of Munich, Munich, Germany.\nGerman Cancer Consortium (DKTK), Partner Site Munich, a partnership between the DKFZ Heidelberg and the University Hospital of the LMU, Heidelberg, Germany.\nEinheit für Klinische Pharmakologie (EKLiP), Helmholtz Zentrum München - German Research Center for Environmental Health, Neuherberg, Germany."
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] | [] | 9.394705 | 4.213645 |
39709851 | 102 | Multi-niche human bone marrow on-a-chip for studying the interactions of adoptive CAR-T cell therapies with multiple myeloma. | Multiple myeloma (MM), a cancer of bone marrow plasma cells, is the second-most common hematological malignancy. However, despite immunotherapies like chimeric antigen receptor (CAR)-T cells, relapse is nearly universal. The bone marrow (BM) microenvironment influences how MM cells survive, proliferate, and resist treatment. Yet, it is unclear which BM niches give rise to MM pathophysiology. Here, we present a 3D microvascularized culture system, which models the endosteal and perivascular bone marrow niches, allowing us to study MM-stroma interactions in the BM niche and model responses to therapeutic CAR-T cells. We demonstrated the prolonged survival of cell line-based and patient-derived multiple myeloma cells within our in vitro system and successfully perfused in donor-matched CAR-T cells. We then measured T cell survival, differentiation, and cytotoxicity against MM cells using a variety of analysis techniques. Our MM-on-a-chip system could elucidate the role of the BM microenvironment in MM survival and therapeutic evasion and inform the rational design of next-generation therapeutics. | [
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] | 2024-12-23 | 1 | 39709851 | [
"MM cells",
"T cell survival",
"bone marrow plasma cells",
"CAR)-T cells",
"MM survival",
"BM niches",
"MM",
"therapeutic CAR-T cells",
"BM",
"therapeutic evasion",
"Multiple myeloma",
"chimeric antigen receptor",
"cell line-based and patient-derived multiple myeloma cells",
"donor-matched CAR-T cells",
"MM-stroma interactions",
"a 3D microvascularized culture system",
"the endosteal and perivascular bone marrow niches",
"MM pathophysiology",
"analysis techniques",
"MM-stroma",
"The bone marrow",
"the BM niche and model responses",
"rise",
"the BM microenvironment",
"cytotoxicity",
"relapse",
"differentiation",
"the prolonged survival",
"immunotherapies",
"next-generation therapeutics"
] | [] | 0 | 10.1016/j.biomaterials.2024.123016 | [
"Ghoshal",
"Petersen",
"Ringquist",
"Kramer",
"Bhatia",
"Hu",
"Richard",
"Park",
"Corbin",
"Agarwal",
"Thomas",
"Ramirez",
"Tharayil",
"Downey",
"Ketchum",
"Ochal",
"Sonthi",
"Lonial",
"Kochenderfer",
"Tran",
"Zhu",
"Lam",
"Coskun",
"Roy"
] | [
"The Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University, Atlanta, GA, 30332, USA; The Parker H. Petit Institute for Bioengineering & Bioscience, Georgia Institute of Technology, Atlanta, GA, 30332, USA.",
"The Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University, Atlanta, GA, 30332, USA; The Parker H. Petit Institute for Bioengineering & Bioscience, Georgia Institute of Technology, Atlanta, GA, 30332, USA.",
"The Parker H. Petit Institute for Bioengineering & Bioscience, Georgia Institute of Technology, Atlanta, GA, 30332, USA; School of Chemical and Biomolecular Engineering, Georgia Institute of Technology, Atlanta, GA, 30332, USA.",
"The Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University, Atlanta, GA, 30332, USA; The Parker H. Petit Institute for Bioengineering & Bioscience, Georgia Institute of Technology, Atlanta, GA, 30332, USA.",
"The Parker H. Petit Institute for Bioengineering & Bioscience, Georgia Institute of Technology, Atlanta, GA, 30332, USA; The George W. Woodruff Department of Mechanical Engineering, Georgia Institute of Technology, Atlanta, GA, 30332, USA.",
"The Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University, Atlanta, GA, 30332, USA; The Parker H. Petit Institute for Bioengineering & Bioscience, Georgia Institute of Technology, Atlanta, GA, 30332, USA; School of Electrical and Computer Engineering, Georgia Institute of Technology, Atlanta, GA, 30332, USA.",
"The Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University, Atlanta, GA, 30332, USA.",
"The Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University, Atlanta, GA, 30332, USA.",
"The Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University, Atlanta, GA, 30332, USA.",
"The Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University, Atlanta, GA, 30332, USA; The Parker H. Petit Institute for Bioengineering & Bioscience, Georgia Institute of Technology, Atlanta, GA, 30332, USA.",
"The Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University, Atlanta, GA, 30332, USA; Department of Biochemistry, Georgia Institute of Technology, Atlanta, GA, 30332, USA.",
"The Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University, Atlanta, GA, 30332, USA.",
"The Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University, Atlanta, GA, 30332, USA.",
"The Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University, Atlanta, GA, 30332, USA.",
"The Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University, Atlanta, GA, 30332, USA; Aerospace and Mechanical Engineering, University of Notre Dame, Notre Dame, IN, 46556, USA.",
"The Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University, Atlanta, GA, 30332, USA.",
"School of Biological Sciences, Georgia Institute of Technology, Atlanta, GA, 30332, USA.",
"Department of Hematology and Medical Oncology, Emory University School of Medicine, Atlanta, GA, 30322, USA.",
"Surgery Branch, National Cancer Institute, Bethesda, MD, 20892, USA.",
"The Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University, Atlanta, GA, 30332, USA; The Parker H. Petit Institute for Bioengineering & Bioscience, Georgia Institute of Technology, Atlanta, GA, 30332, USA; Division of Pediatric Hematology/Oncology, Department of Pediatrics, Aflac Cancer Center and Blood Disorders Service of Children's Healthcare of Atlanta, Emory University School of Medicine, Atlanta, GA, 30322, USA.",
"The Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University, Atlanta, GA, 30332, USA.",
"The Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University, Atlanta, GA, 30332, USA; The Parker H. Petit Institute for Bioengineering & Bioscience, Georgia Institute of Technology, Atlanta, GA, 30332, USA; Division of Pediatric Hematology/Oncology, Department of Pediatrics, Aflac Cancer Center and Blood Disorders Service of Children's Healthcare of Atlanta, Emory University School of Medicine, Atlanta, GA, 30322, USA.",
"The Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University, Atlanta, GA, 30332, USA; The Parker H. Petit Institute for Bioengineering & Bioscience, Georgia Institute of Technology, Atlanta, GA, 30332, USA.",
"School of Engineering, Vanderbilt University, Nashville, TN, 37235, USA. Electronic address: [email protected]."
] | [
"39709851"
] | [] | 4.829502 | 6.291785 |
39702149 | 103 | MDSC: a new potential breakthrough in CAR-T therapy for solid tumors. | Chimeric antigen receptor T (CAR-T) cell therapy has shown remarkable success in hematologic malignancies but has encountered challenges in effectively treating solid tumors. One major obstacle is the presence of the immunosuppressive tumor microenvironment (TME), which is mainly built by myeloid-derived suppressor cells (MDSCs). Recent studies have shown that MDSCs have a detrimental effect on CAR-T cells due to their potent immunosuppressive capabilities. Targeting MDSCs has shown promising results to enhance CAR-T immunotherapy in preclinical solid tumor models. In this review, we first highlight that MDSCs increase tumor proliferation, transition, angiogenesis and encourage circulating tumor cells (CTCs) extravasation leading to tumor progression and metastasis. Moreover, we describe the main characteristics of the immunosuppressive activities of MDSCs on T cells in TME. Most importantly, we summarize targeting therapeutic strategies of MDSCs in CAR-T therapies against solid tumors. These strategies include (1) therapeutic targeting of MDSCs through small molecule inhibitors and large molecule antibodies; (2) CAR-T targeting cancer cell antigen combination with MDSC modulatory agents; (3) cytokine receptor antigen-targeted CAR-T indirectly or directly targeting MDSCs reshapes TME; (4) modified natural killer (NK) cells expressing activating receptor directly targeting MDSCs; and (5) CAR-T directly targeting MDSC selective antigens. In the near future, we are expected to witness the improvement of CAR-T cell therapies for solid tumors by targeting MDSCs in clinical practice. | [
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] | 2024-12-20 | 150 | 39702149 | [
"Targeting MDSCs",
"circulating tumor cells",
"T cells",
"solid tumors",
"MDSCs reshapes",
"cancer cell antigen combination",
"preclinical solid tumor models",
"MDSCs",
"tumor proliferation",
"tumor progression",
"CAR-T cell therapies",
"CAR-T cells",
"activating receptor",
"MDSC selective antigens",
"MDSC modulatory agents",
"small molecule inhibitors",
"CAR-T therapies",
"therapeutic strategies",
"myeloid-derived suppressor cells",
"the immunosuppressive tumor microenvironment",
"TME",
"CAR-T immunotherapy",
"large molecule",
"hematologic malignancies",
"remarkable success",
"promising results",
"CAR-T",
"MDSC",
"Recent studies",
"clinical practice"
] | [
"Chimeric antigen receptor T (CAR-T)",
"Myeloid-derived suppressor cells (MDSCs)",
"Solid tumor",
"Tumor microenvironment (TME)"
] | 0 | 10.1186/s12964-024-01995-y | [
"Abdalsalam",
"Ibrahim",
"Saliu",
"Liu",
"Wan",
"Yan"
] | [
"Guangdong Immune Cell Therapy Engineering and Technology Research Center, Center for Protein and Cell-Based Drugs, Institute of Biomedicine and Biotechnology, Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, Shenzhen, 518055, China.\nUniversity of Chinese Academy of Sciences, Beijing, 100864, China.",
"Guangdong Immune Cell Therapy Engineering and Technology Research Center, Center for Protein and Cell-Based Drugs, Institute of Biomedicine and Biotechnology, Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, Shenzhen, 518055, China.\nUniversity of Chinese Academy of Sciences, Beijing, 100864, China.",
"Guangdong Immune Cell Therapy Engineering and Technology Research Center, Center for Protein and Cell-Based Drugs, Institute of Biomedicine and Biotechnology, Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, Shenzhen, 518055, China.\nUniversity of Chinese Academy of Sciences, Beijing, 100864, China.",
"Institute of Translational Medicine, Faculty of Health Sciences, University of Macau, Macao SAR, Taipa, China. [email protected].",
"Guangdong Immune Cell Therapy Engineering and Technology Research Center, Center for Protein and Cell-Based Drugs, Institute of Biomedicine and Biotechnology, Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, Shenzhen, 518055, China. [email protected].\nUniversity of Chinese Academy of Sciences, Beijing, 100864, China. [email protected].",
"Guangdong Immune Cell Therapy Engineering and Technology Research Center, Center for Protein and Cell-Based Drugs, Institute of Biomedicine and Biotechnology, Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, Shenzhen, 518055, China. [email protected].\nUniversity of Chinese Academy of Sciences, Beijing, 100864, China. [email protected]."
] | [
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] | [] | 9.999554 | 5.144986 |
39701037 | 104 | Microengineered in vitro CAR T cell screens and assays. | Established and emergent microengineered in vitro systems enable the evaluation of chimeric antigen receptor (CAR) T cell product purity, avidity, and functionality. Here, we describe such systems and how they have been used to optimize CAR T cell products by selecting highly viable cells, eliminating off-target cells, and tailoring avidity to balance efficacy and safety. The future of CAR T cell therapy development and manufacturing is expected to be anchored in a cyclical process that integrates multiple high-throughput and patient-centered techniques for identifying, enriching, and evaluating T cell subtypes. This article explores several cutting-edge platforms and methodologies relevant to these processes. | [
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] | 2024-12-20 | 1 | 39701037 | [
"CAR T cell therapy development",
"such systems",
"CAR T cell products",
"chimeric antigen receptor",
"T cell subtypes",
"CAR) T cell product purity",
"avidity",
"several cutting-edge platforms",
"highly viable cells",
"methodologies",
"identifying",
"manufacturing",
"target",
"efficacy",
"a cyclical process",
"safety",
"functionality",
"vitro systems",
"multiple high-throughput and patient-centered techniques",
"these processes",
"the evaluation",
"This article",
"The future",
"that",
"they",
"we"
] | [
"CAR T",
"T cell",
"immunotherapy",
"in vitro system",
"microfluidic system"
] | 0 | 10.1016/j.cels.2024.11.011 | [
"Kim",
"Thomas"
] | [
"George W. Woodruff School of Mechanical Engineering, Georgia Institute of Technology, Atlanta, GA 30332, USA.",
"George W. Woodruff School of Mechanical Engineering, Georgia Institute of Technology, Atlanta, GA 30332, USA; Parker H. Petit Institute for Bioengineering and Bioscience, Georgia Institute of Technology, Atlanta, GA 30332, USA; Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University, Atlanta, GA 30332, USA; Winship Cancer Institute, Emory University, Atlanta, GA 30322, USA. Electronic address: [email protected]."
] | [
"39701037"
] | [] | 8.560524 | 3.228625 |
39700677 | 105 | Advances in chimeric antigen receptor T cell therapy for autoimmune and autoinflammatory diseases and their complications. | Chimeric antigen receptor T (CAR-T) cells are genetically engineered T cells expressing transmembrane chimeric antigen receptors with specific targeting abilities. As an emerging immunotherapy, the use of CAR-T cells has made significant breakthroughs in cancer treatment, particularly for hematological malignancies. The success of CAR-T cell therapy in blood cancers highlights its potential for other conditions in which the clearance of pathological cells is therapeutic, such as liver diseases, infectious diseases, heart failure, and diabetes. Given the limitations of current therapies for autoimmune diseases, researchers have actively explored the potential therapeutic value of CAR-T cells and their derivatives in the field of autoimmune diseases. This review focuses on the research progress and current challenges of CAR-T cells in autoimmune diseases with the aim of providing a theoretical basis for the precise treatment of autoimmune diseases. In the future, CAR-T cells may present new therapeutic modalities and ultimately provide hope for patients with autoimmune diseases. | [
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] | 2024-12-20 | 1 | 39700677 | [
"autoimmune diseases",
"pathological cells",
"liver diseases",
"infectious diseases",
"transmembrane chimeric antigen receptors",
"new therapeutic modalities",
"CAR-T cell therapy",
"current therapies",
"cancer treatment",
"CAR-T cells",
"blood cancers",
"genetically engineered T cells",
"current challenges",
"other conditions",
"specific targeting abilities",
"Chimeric antigen receptor T (CAR-T) cells",
"significant breakthroughs",
"heart failure",
"hematological malignancies",
"the potential therapeutic value",
"hope",
"researchers",
"patients",
"the precise treatment",
"the research progress",
"a theoretical basis",
"an emerging immunotherapy",
"its potential",
"the clearance",
"the aim"
] | [
"Autoimmune diseases",
"Chimeric antigen receptor T cells",
"Chimeric autoantibody receptor T cells"
] | 0 | 10.1016/j.jaut.2024.103350 | [
"Zeng",
"Li",
"Xiang",
"Xiao",
"Long",
"Sun"
] | [
"Department of Rheumatology and Immunology, Nanjing Drum Tower Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Graduate School of Peking Union Medical College, Nanjing, China. Electronic address: [email protected].",
"People's Hospital of Ningxiang City, Ningxiang City, China.",
"Department of Rheumatology, Changde Hospital, Xiangya School of Medicine, Central South University (The First People's Hospital of Changde City), Changde City, China.",
"Department of Rheumatology, Changde Hospital, Xiangya School of Medicine, Central South University (The First People's Hospital of Changde City), Changde City, China. Electronic address: [email protected].",
"Department of Physical Medicine and Rehabilitation, The Affiliated Panyu Central Hospital of Guangzhou Medical University, Guangzhou, China.",
"Department of Rheumatology and Immunology, Nanjing Drum Tower Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Graduate School of Peking Union Medical College, Nanjing, China; Department of Rheumatology and Immunology, The First Affiliated Hospital of Anhui Medical University, Hefei, China. Electronic address: [email protected]."
] | [
"39700677"
] | [] | 7.865645 | 4.183488 |
39697716 | 106 | Immunotherapy for locally advanced and metastatic basal cell carcinoma: a narrative review. | Basal cell carcinoma (BCC) is the most common malignancy of humankind, characterized by its low propensity for metastasis and its high recurrence rate. Surgical intervention is the predominant therapeutic approach. However, for cases of locally advanced BCC (laBCC) and metastatic BCC (mBCC), systematic therapy may be the first option. In recent years, tumor immunotherapy has garnered significant attention within the scientific community. And it has progressively demonstrated its efficacy in the treatment of laBCC and mBCC. This review aims to summarize the characteristics of immune microenvironment, biomarkers, and immunotherapies of BCC, and provide a reference for further research on BCC immunotherapy.
We searched literature in PubMed database and Web of Science and considered all study types written in English from 2013 to 2024.
The alteration of the immune microenvironment is a pivotal factor in the progression of BCC. The expression levels of sex determining region Y (SRY)-box 2 (SOX2) and matrix metalloproteinases (MMPs) have emerged as potential prognostic biomarkers for BCC. And they are promising therapeutic targets for laBCC and mBCC. For patients presenting with laBCC or mBCC, a spectrum of immunotherapeutic approaches is being explored, including inhibition of the programmed death receptor 1 (PD-1) and programmed death ligand 1 (PD-L1), blockade of cytotoxic T-lymphocyte antigen 4 (CTLA-4), lymphocyte activation gene 3 (LAG-3) inhibition therapy, the use of chimeric antigen receptor (CAR)-T cells, and vaccination. Cemiplimab is the first immune checkpoint inhibitor (ICI) approved by the Food and Drug Administration for refractory BCC, marking a major breakthrough in BCC immunotherapy.
Immunotherapies have shown efficacy in clinical studies. In the future, more multicenter studies with large samples are needed to further explore the efficacy and safety of immunotherapy for BCC. | [
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"BCC immunotherapy",
"refractory BCC",
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"significant attention",
"mBCC",
"large samples",
"inhibition",
"biomarkers",
"locally advanced BCC",
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] | [
"Basal cell carcinoma (BCC)",
"biomarker",
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10.1097/CJI.0000000000000237 | [
"Li",
"Wang",
"Lu"
] | [
"Department of Dermatology, The First Affiliated Hospital of Jinan University, Guangzhou, China.\nDepartment of Dermatology, Binhaiwan Central Hospital of Dongguan, Dongguan, China.",
"Department of Dermatology, The First Affiliated Hospital of Jinan University, Guangzhou, China.",
"Department of Dermatology, Binhaiwan Central Hospital of Dongguan, Dongguan, China.\nThe First Clinical Medical College of Jinan University, Guangzhou, China."
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] | [] | 10.962082 | 4.449533 |
39697210 | 107 | The current socioeconomic and regulatory landscape of immune effector cell therapies. | Immune cell effector therapies, including chimeric antigen receptor (CAR)-T cells, T-cell receptor (TCR) T cells, natural killer (NK) cells, and macrophage-based therapies, represent a transformative approach to cancer treatment, harnessing the immune system to target and eradicate malignant cells. CAR-T cell therapy, the most established among these, involves engineering T cells to express CARs specific to cancer cell antigens, showing remarkable efficacy in hematologic malignancies like leukemias, B-cell lymphomas, and multiple myeloma. Similarly, TCR-modified therapies, which reprogram T cells to recognize intracellular tumor antigens presented by major histocompatibility complex (MHC) molecules, offer promise for a range of solid tumors. NK-cell therapies leverage NK cells' innate cytotoxicity, providing an allogeneic approach that avoids some of the immune-related complications associated with T-cell-based therapies. Macrophage-based therapies, still in early stages of the development, focus on reprogramming macrophages to stimulate an immune response against cancer cells in the tumor microenvironment. Despite their promise, socioeconomic and regulatory challenges hinder the accessibility and scalability of immune cell effector therapies. These treatments are costly, with CAR-T therapies currently exceeding $400,000 per patient, creating significant disparities in access based on socioeconomic status and geographic location. The high manufacturing costs stem from the personalized, labor-intensive processes of harvesting, modifying, and expanding patients' cells. Moreover, complex logistics for manufacturing and delivering these therapies limit their reach, particularly in low-resource settings. Regulatory pathways further complicate the landscape. In the United States., the Food and Drug Administrations' (FDA) accelerated approval processes for cell-based therapies facilitate innovation but do not address cost-related barriers. In Europe, the European Medicines Agency (EMA) offers adaptive pathways, yet decentralized reimbursement systems create uneven access across member states. Additionally, differing regulatory standards for manufacturing and quality control worldwide pose hurdles for global harmonization and access. To expand the reach of immune effector cell therapies, a multipronged approach is needed-streamlined regulatory frameworks, policies to reduce treatment costs, and international collaborations to standardize manufacturing. Addressing these socioeconomic and regulatory obstacles is essential to make these life-saving therapies accessible to a broader patient population worldwide. We present a literature review on the current landscape of immune effector cell therapies and barriers of access to currently approved standard of care therapy at various levels. | [
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10.1136/jitc-2022-005755 | [
"Sainatham",
"Yadav",
"Dilli Babu",
"Tallapalli",
"Kanagala",
"Filippov",
"Murillo Chavez",
"Ahmed",
"Lutfi"
] | [
"Department of Internal Medicine, Sinai Hospital of Baltimore, Baltimore, MD, United States.",
"Department of Internal Medicine, Sinai Hospital of Baltimore, Baltimore, MD, United States.",
"Department of Internal Medicine, Sinai Hospital of Baltimore, Baltimore, MD, United States.",
"Division of Infectious Diseases, Department of Internal Medicine, University of South Florida, Tampa, FL, United States.",
"Department of Internal Medicine, New York Medical College/Metropolitan Hospital Center, New York, NY, United States.",
"Department of Internal Medicine, Sinai Hospital of Baltimore, Baltimore, MD, United States.",
"Department of Internal Medicine, Sinai Hospital of Baltimore, Baltimore, MD, United States.",
"Department of Hematologic Malignancies and Cellular Therapeutics, University of Kansas Medical Center, Kansas City, KS, United States.",
"Department of Hematologic Malignancies and Cellular Therapeutics, University of Kansas Medical Center, Kansas City, KS, United States."
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39695851 | 108 | Tumor-derived G-CSF induces an immunosuppressive microenvironment in an osteosarcoma model, reducing response to CAR.GD2 T-cells. | Sarcomas are rare, mesenchymal tumors, representing about 10-15% of all childhood cancers. GD2 is a suitable target for chimeric antigen receptor (CAR) T-cell therapy due to its overexpression in several solid tumors. In this preclinical study, we investigated the potential use of iCasp9.2A.GD2.CAR-CD28.4-1BBζ (CAR.GD2) T-cells as a treatment option for patients who have GD2-positive sarcomas and we sought to identify factors shaping hostile tumor microenvironment in this setting. GD2 expression was evaluated by flow-cytometry on primary tumor biopsies of pediatric sarcoma patients. GD2 expression in sarcoma cells was also evaluated in response to an enhancer of zeste homolog 2 (EZH2) inhibitor (Tazemetostat). The antitumor activity of CAR.GD2 T-cells was evaluated both in vitro and in vivo preclinical models of orthotopic and/or metastatic soft-tissue and bone sarcomas. GD2 expression was detected in 55% of the primary tumors. Notably, the Osteosarcoma and Alveolar Rhabdomyosarcomas subtypes exhibited the highest GD2 expression levels, while Ewing sarcoma showed the lowest. CAR.GD2 T-cells show a significant tumor control both in vitro and in vivo models of GD2-expressing tumors. Pretreatment with an EZH2 inhibitor (Tazemetostat) upregulating GD2 expression, sensitizes GD2 | [
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] | 0 | 10.1186/s13045-024-01641-7 | [
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"Department of Onco-Haematology and Cell and Gene Therapy, Bambino Gesù Children's Hospital, IRCCS, San Paolo N°15 Street, 00146, Rome, Italy.",
"Department of Onco-Haematology and Cell and Gene Therapy, Bambino Gesù Children's Hospital, IRCCS, San Paolo N°15 Street, 00146, Rome, Italy.\nDepartment of Clinical Medicine and Surgery, Federico II University of Naples, 80131, Naples, Italy.",
"Department of Onco-Haematology and Cell and Gene Therapy, Bambino Gesù Children's Hospital, IRCCS, San Paolo N°15 Street, 00146, Rome, Italy.\nDepartment of Molecular Medicine, Sapienza University of Rome, 00185, Rome, Italy.",
"Department of Onco-Haematology and Cell and Gene Therapy, Bambino Gesù Children's Hospital, IRCCS, San Paolo N°15 Street, 00146, Rome, Italy.\nPhD Program in Immunology, Molecular Medicine and Applied Biotechnologies, Faculty of Medicine, University of Rome Tor Vergata, 00173, Rome, Italy.",
"Department of Onco-Haematology and Cell and Gene Therapy, Bambino Gesù Children's Hospital, IRCCS, San Paolo N°15 Street, 00146, Rome, Italy.",
"Department of Onco-Haematology and Cell and Gene Therapy, Bambino Gesù Children's Hospital, IRCCS, San Paolo N°15 Street, 00146, Rome, Italy.",
"Department of Onco-Haematology and Cell and Gene Therapy, Bambino Gesù Children's Hospital, IRCCS, San Paolo N°15 Street, 00146, Rome, Italy.",
"Department of Onco-Haematology and Cell and Gene Therapy, Bambino Gesù Children's Hospital, IRCCS, San Paolo N°15 Street, 00146, Rome, Italy.",
"Department of Onco-Haematology and Cell and Gene Therapy, Bambino Gesù Children's Hospital, IRCCS, San Paolo N°15 Street, 00146, Rome, Italy.",
"Department of Onco-Haematology and Cell and Gene Therapy, Bambino Gesù Children's Hospital, IRCCS, San Paolo N°15 Street, 00146, Rome, Italy.",
"Department of Onco-Haematology and Cell and Gene Therapy, Bambino Gesù Children's Hospital, IRCCS, San Paolo N°15 Street, 00146, Rome, Italy.",
"Department of Onco-Haematology and Cell and Gene Therapy, Bambino Gesù Children's Hospital, IRCCS, San Paolo N°15 Street, 00146, Rome, Italy.",
"Department of Onco-Haematology and Cell and Gene Therapy, Bambino Gesù Children's Hospital, IRCCS, San Paolo N°15 Street, 00146, Rome, Italy.",
"Department of Onco-Haematology and Cell and Gene Therapy, Bambino Gesù Children's Hospital, IRCCS, San Paolo N°15 Street, 00146, Rome, Italy.\nDepartment of Molecular Medicine, Sapienza University of Rome, 00185, Rome, Italy.",
"Department of Onco-Haematology and Cell and Gene Therapy, Bambino Gesù Children's Hospital, IRCCS, San Paolo N°15 Street, 00146, Rome, Italy.",
"Department of Onco-Haematology and Cell and Gene Therapy, Bambino Gesù Children's Hospital, IRCCS, San Paolo N°15 Street, 00146, Rome, Italy.",
"Department of Onco-Haematology and Cell and Gene Therapy, Bambino Gesù Children's Hospital, IRCCS, San Paolo N°15 Street, 00146, Rome, Italy.",
"Department of Onco-Haematology and Cell and Gene Therapy, Bambino Gesù Children's Hospital, IRCCS, San Paolo N°15 Street, 00146, Rome, Italy.",
"Department of Onco-Haematology and Cell and Gene Therapy, Bambino Gesù Children's Hospital, IRCCS, San Paolo N°15 Street, 00146, Rome, Italy.",
"Department of Onco-Haematology and Cell and Gene Therapy, Bambino Gesù Children's Hospital, IRCCS, San Paolo N°15 Street, 00146, Rome, Italy.",
"Unit of Pathogen Specific Immunity, Bambino Gesù Children's Hospital, IRCCS, 00145, Rome, Italy.",
"Unit of Pathogen Specific Immunity, Bambino Gesù Children's Hospital, IRCCS, 00145, Rome, Italy.",
"Unit of Pathogen Specific Immunity, Bambino Gesù Children's Hospital, IRCCS, 00145, Rome, Italy.",
"Department of Onco-Haematology and Cell and Gene Therapy, Bambino Gesù Children's Hospital, IRCCS, San Paolo N°15 Street, 00146, Rome, Italy.",
"Department of Onco-Haematology and Cell and Gene Therapy, Bambino Gesù Children's Hospital, IRCCS, San Paolo N°15 Street, 00146, Rome, Italy.",
"Department of Onco-Haematology and Cell and Gene Therapy, Bambino Gesù Children's Hospital, IRCCS, San Paolo N°15 Street, 00146, Rome, Italy.",
"Department of Onco-Haematology and Cell and Gene Therapy, Bambino Gesù Children's Hospital, IRCCS, San Paolo N°15 Street, 00146, Rome, Italy.",
"Department of Onco-Haematology and Cell and Gene Therapy, Bambino Gesù Children's Hospital, IRCCS, San Paolo N°15 Street, 00146, Rome, Italy.",
"Department of Onco-Haematology and Cell and Gene Therapy, Bambino Gesù Children's Hospital, IRCCS, San Paolo N°15 Street, 00146, Rome, Italy. [email protected].\nDepartment of Life Sciences and Public Health, Catholic University of the Sacred Heart, S. Onofrio Square, 00165, Rome, Italy. [email protected].",
"Department of Onco-Haematology and Cell and Gene Therapy, Bambino Gesù Children's Hospital, IRCCS, San Paolo N°15 Street, 00146, Rome, Italy. [email protected]."
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39695004 | 109 | Clinical progress in the development of CAR T cells to treat malignant glioma. | Chimeric antigen receptor (CAR) T cell therapy is an exciting modality of immunotherapy that has revolutionized the treatment of hematologic malignancies. However, translating this success to malignant gliomas such as glioblastoma (GBM) and diffuse midline glioma (DMG) remains a formidable challenge due to multiple biologic, anatomic, and immunologic factors. Despite these hurdles, a number of clinical trials deployed over the last decade have increased optimism for the potential of CAR T cell therapy in glioma treatment.
We highlight historical and ongoing clinical trials of CAR T cell therapy in glioma, with a focus on key tumor-associated antigens such as IL-13Rα2, HER2, EGFR, EGFRvIII, EphA2, GD2, and B7-H3. Early studies established proof-of-concept for antigen-specific CAR T cell targeting, yet immune evasion mechanisms such as antigen downregulation and limited CAR T cell persistence remain significant obstacles. Recent approaches, including multiantigen targeting, alternative cell sources, and innovations in delivery routes offer promising strategies to overcome these challenges.
The rapid evolution of investigational CAR T cell therapies portends great potential for the future of glioma treatment. Future studies will need to refine antigen targeting strategies, optimize CAR T cell persistence, and integrate combinatorial approaches to fully harness the therapeutic potential of this modality and improve the therapeutic window against brain tumors. | [
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] | 0 | 10.1007/s11060-024-04909-7
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10.1136/jitc-2023-SITC2023.1525 | [
"Grewal",
"Nahed",
"Carter",
"Gerstner",
"Curry",
"Maus",
"Choi"
] | [
"Brain Tumor Immunotherapy Laboratory, Massachusetts General Hospital, Boston, MA, USA.\nDepartment of Pathology, Massachusetts General Hospital, Boston, MA, USA.",
"Department of Neurosurgery, Massachusetts General Hospital, Boston, MA, USA.",
"Department of Neurosurgery, Massachusetts General Hospital, Boston, MA, USA.",
"Department of Neurology, Massachusetts General Hospital, Boston, MA, USA.",
"Brain Tumor Immunotherapy Laboratory, Massachusetts General Hospital, Boston, MA, USA.\nDepartment of Neurosurgery, Massachusetts General Hospital, Boston, MA, USA.",
"Cellular Immunotherapy Program, Massachusetts General Hospital, Boston, MA, USA.",
"Brain Tumor Immunotherapy Laboratory, Massachusetts General Hospital, Boston, MA, USA. [email protected].\nDepartment of Neurosurgery, Massachusetts General Hospital, Boston, MA, USA. [email protected].\nCellular Immunotherapy Program, Massachusetts General Hospital, Boston, MA, USA. [email protected]."
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39694704 | 110 | Preclinical development of three novel CARs targeting CD79b for the treatment of non-Hodgkin's lymphoma and characterization of the loss of the target antigen. | Infusion of T cells modified with a chimeric antigen receptor (CAR) targeting CD19 has achieved exceptional responses in patients with non-Hodgkin's lymphoma (NHL), which led to the approval of CAR targeting CD19 (CART19) (Axi-cel and Liso-cel) as second line of treatment for adult patients with relapsed/refractory NHL. Unfortunately, 60% of patients still relapse after CART19 due to either a loss of expression of the target antigen (CD19) in the tumor cell, observed in 27% of relapsed patients, a limited CAR-T persistence, and additional mechanisms, including the suppression of the tumor microenvironment. Clinic strategies to prevent target antigen loss include sequential treatment with CARs directed at CD20 or CD22, which have caused loss of the second antigen, suggesting targeting other antigens less prone to disappear. CD79b, expressed in NHL, is a target in patients treated with antibody-drug conjugates (ADC). However, the limited efficacy of ADC suggests that a CAR therapy targeting CD79b might improve results.
We designed three new CARs against CD79b termed CAR for Lymphoma (CARLY)1, 2 and 3. We compared their efficacy, phenotype, and inflammatory profiles with CART19 (ARI0001) and CARTBCMA (ARI0002h), which can treat NHL. We also analyzed the target antigen's expression loss (CD79b, CD19, and B-cell maturation antigen(BCMA)).
We found that CARLY2 and CARLY3 had high affinity and specificity towards CD79b on B cells. In vitro, all CAR-T cells had similar anti-NHL efficacy, which was retained in an NHL model of CD19
Based on specificity, efficacy, and loss of the target antigen, CARLY3 represents a potential novel CAR treatment for NHL. | [
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10.1038/s41375-022-01585-2 | [
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"Serrano-Lopez",
"Juan",
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"Department of Experimental Hematology, Health Research Institute of the Jimenez Diaz Foundation, UAM, Madrid, Spain, UAM, Madrid, Spain.\nNext Generation CART MAD Consortium, Madrid, Spain.\nDepartamento de Desarrollo de Medicamentos de Terapias Avanzadas, Instituto de Salud Carlos III, Madrid, Spain.",
"Department of Experimental Hematology, Health Research Institute of the Jimenez Diaz Foundation, UAM, Madrid, Spain, UAM, Madrid, Spain.",
"Department of Experimental Hematology, Health Research Institute of the Jimenez Diaz Foundation, UAM, Madrid, Spain, UAM, Madrid, Spain.",
"Department of Experimental Hematology, Health Research Institute of the Jimenez Diaz Foundation, UAM, Madrid, Spain, UAM, Madrid, Spain.",
"Department of Experimental Hematology, Health Research Institute of the Jimenez Diaz Foundation, UAM, Madrid, Spain, UAM, Madrid, Spain.",
"Department of Immunology, Instituto de Investigación Sanitaria Fundación Jiménez Díaz, UAM, Madrid, Spain.",
"Department of Biomedical Science, University of Barcelona Faculty of Medicine and Health Sciences, Barcelona, Spain.",
"Josep Carreras Leukaemia Research Institute, Barcelona, Spain.",
"Department of Experimental Hematology, Health Research Institute of the Jimenez Diaz Foundation, UAM, Madrid, Spain, UAM, Madrid, Spain.\nNext Generation CART MAD Consortium, Madrid, Spain.",
"Hospital Clínic de Barcelona, IDIBAPS, Universidad de Barcelona, Barcelona, Spain.",
"Department of Biomedical Science, University of Barcelona Faculty of Medicine and Health Sciences, Barcelona, Spain.",
"Department of Experimental Hematology, Health Research Institute of the Jimenez Diaz Foundation, UAM, Madrid, Spain, UAM, Madrid, Spain.\nNext Generation CART MAD Consortium, Madrid, Spain.",
"Department of Experimental Hematology, Health Research Institute of the Jimenez Diaz Foundation, UAM, Madrid, Spain, UAM, Madrid, Spain.\nNext Generation CART MAD Consortium, Madrid, Spain.",
"Department of Experimental Hematology, Health Research Institute of the Jimenez Diaz Foundation, UAM, Madrid, Spain, UAM, Madrid, Spain [email protected].\nNext Generation CART MAD Consortium, Madrid, Spain.\nDepartamento de Desarrollo de Medicamentos de Terapias Avanzadas, Instituto de Salud Carlos III, Madrid, Spain."
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39693800 | 111 | Nucleotide receptor P2X7/STAT6 pathway regulates macrophage M2 polarization and its application in CAR-T immunotherapy. | A key factor underlying the failure of Chimeric Antigen Receptor-T Cell (CAR-T) therapy in ovarian cancer (OC) is the presence of an immunosuppressive tumor microenvironment, which is intricately linked to M2 polarization among tumor-infiltrating macrophages. P2X7 receptor has been previously documented as expressed within these macrophages and its correlation with M2 polarization is evident. This investigation scrutinizes whether silencing of P2X7 receptor within macrophages could lead to augmented anti-tumor potency of CAR-T.
Human peripheral blood mononuclear cells were artificially differentiated into macrophages or M2 macrophage in vitro. After silencing P2X7 receptor and/or overexpressing STAT6 within macrophages, the M1 and M2 markers were evaluated via flow cytometry, ELISA, and qRT-PCR. Additionally, the phosphorylation level of STAT6 was monitored by western blot. We engineered CAR-T cells targeting the non-functional P2X7 (nfP2X7) receptor, and co-cultured them with macrophages silencing P2X7 receptor along with OC cells. The anti-tumor effect of these CAR-T cells was assessed through evaluating OC cell viability, lactate dehydrogenase release, and IFN-γ levels.
P2X7 receptor silencing promotes M1 macrophage marker expression (CD86, TNF-α, IL-6, IL-1β), diminishes M2 macrophage marker expression (CD206 and IL-10) and suppresses STAT6 phosphorylation, whereas STAT6 overexpression reverses these phenomena. Furthermore, M2 macrophage suppresses the toxic effect of CAR-T cells on OC cells, while silencing the P2X7 receptor nullifies the immunosuppressive effect of M2 macrophages on CAR-T cells.
Silencing P2X7 receptor can reverse M2 macrophage polarization by suppressing STAT6 activation, thereby enhancing the anti-tumor efficacy of CAR-T cells targeting nfP2X7 receptor in OC cell lines. | [
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"CAR-T.\nHuman peripheral blood mononuclear cells",
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] | [
"Chimeric antigen receptor T",
"M2 macrophage",
"Ovarian cancer",
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] | 0 | 10.1016/j.imbio.2024.152863 | [
"Si",
"Yang",
"Liu",
"Liu",
"Bu",
"Cui"
] | [
"the Inner Mongolia Key Laboratory for Molecular Regulation of the Cell and the State Key Laboratory of Reproductive Regulation, School of Life Sciences, Inner Mongolia University, Hohhot 010010, Inner Mongolia Autonomous Region, P.R. China.",
"Department of Gyneacological Oncology, Peking University Cancer Hospital (Inner Mongolia Campus)/Affiliated Cancer Hospital of Inner Mongolia Medical University, Hohhot 010010, Inner Mongolia Autonomous Region, P.R. China.",
"Department of Ultrasound, International Mongolian Hospital of Inner Mongolia, Hohhot 010020, Inner Mongolia Autonomous Region, P.R. China.",
"Department of Gyneacological Oncology, Peking University Cancer Hospital (Inner Mongolia Campus)/Affiliated Cancer Hospital of Inner Mongolia Medical University, Hohhot 010010, Inner Mongolia Autonomous Region, P.R. China.",
"Department of Gyneacological Oncology, Peking University Cancer Hospital (Inner Mongolia Campus)/Affiliated Cancer Hospital of Inner Mongolia Medical University, Hohhot 010010, Inner Mongolia Autonomous Region, P.R. China.",
"Research Service Office, Peking University Cancer Hospital (Inner Mongolia Campus)/Affiliated Cancer Hospital of Inner Mongolia Medical, Hohhot 010010, Inner Mongolia Autonomous Region, P.R. China. Electronic address: [email protected]."
] | [
"39693800"
] | [] | 10.157298 | 5.962448 |
39692673 | 112 | Efficacy of chimeric antigen receptor engineered natural killer cells in the treatment of hematologic malignancies: a systematic review and meta-analysis of preclinical studies. | Chimeric antigen receptor (CAR) engineered NK cells (CAR-NK) are a novel approach to the immunotherapy of hematologic malignancies which seeks to overcome some of the challenges faced by CAR-T cells (CAR-T). With few published clinical studies, preclinical studies can identify strategies to accelerate clinical translation. We conducted a systematic review on the preclinical in vivo use of CAR-NK for the treatment of hematologic malignancies to assess these therapies in a holistic and unbiased manner.
Our protocol was registered with PROSPERO (ID: CRD42023438375). We performed a search of OVID MEDLINE, OVID Embase, and Embase for animal studies employing human CAR-NK cells in the treatment of hematologic malignancies. Screening of studies for eligibility criteria was performed in duplicate. Our primary outcomes were survival and reduction in tumor volume. Data extraction from individual experiments was performed by one reviewer using Digitizeit
A total of 34 papers met eligibility criteria. Overall, CD19 was the most common antigen targeted however there was substantial diversity in antigenic targets, source material for generating CAR-NK cells, and NK cell modifications. Mice treated with CAR-NK therapy survived significantly longer than untreated mice (median survival ratio of 1.18, 95% CI: 1.10-1.27, P < 0.001), and mice treated with nonengineered NK cells (median survival ratio 1.13, 95% CI: 1.03-1.23, P < 0.001). Similarly, treatment with CAR-NK significantly reduced the tumor burden when compared to untreated mice (ratio of mean tumor volume 0.23, 95% CI: 0.17-0.32, P < 0.001) or mice treated with nonengineered NK cells (ratio of mean tumor volume 0.37, 95% CI: 0.28-0.51, P < 0.001). Subgroup analysis showed that cotreatment with IL-15 reduced tumor volume but did not increase survival. In general, CAR-NK cell persistence was short but was increased by IL-15.
CAR-NK shows promise for the treatment of hematologic malignancies in preclinical models. | [
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] | 2024-12-18 | 1 | 39692673 | [
"NK cells",
"nonengineered NK cells",
"NK cell modifications",
"hematologic malignancies",
"mean tumor volume",
"tumor volume",
"preclinical studies",
"median survival ratio",
"few published clinical studies",
"animal studies",
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"human CAR-NK cells",
"studies",
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"CAR",
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"Mice",
"mice",
"eligibility criteria",
"Chimeric antigen receptor",
"ratio",
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"OVID MEDLINE",
"individual experiments",
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] | [
"CAR-NK",
"acute leukemia",
"cell therapy",
"hematologic malignancy",
"immunotherapy",
"lymphoma",
"multiple myeloma",
"preclinical systematic review"
] | 0 | 10.1016/j.jcyt.2024.11.004 | [
"Bastin",
"Kilgour",
"Shorr",
"Sabri",
"Delluc",
"Ardolino",
"McComb",
"Lee",
"Allan",
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] | [
"Department of Medicine, University of Ottawa, Ottawa, Ontario, Canada.",
"Cancer Research, Ottawa Hospital Research Institute, Ottawa, Ontario, Canada.",
"Learning Services, The Ottawa Hospital, Ottawa, Ontario, Canada.",
"Methods Centre, Ottawa Hospital Research Institute, Ottawa, Ontario, Canada.",
"Department of Medicine (Hematology), The Ottawa Hospital, Ottawa, Ontario, Canada.",
"Department of Medicine, University of Ottawa, Ottawa, Ontario, Canada; Cancer Research, Ottawa Hospital Research Institute, Ottawa, Ontario, Canada; Department of Biochemistry, Microbiology and Immunology, University of Ottawa, Ottawa, Ontario, Canada; CI3, University of Ottawa, Ottawa, Ontario, Canada.",
"Human Health Therapeutics Research Center, National Research Council, Ottawa, Ontario, Canada.",
"Department of Biochemistry, Microbiology and Immunology, University of Ottawa, Ottawa, Ontario, Canada.",
"Department of Medicine (Hematology), The Ottawa Hospital, Ottawa, Ontario, Canada.",
"Methods Centre, Ottawa Hospital Research Institute, Ottawa, Ontario, Canada; School of Epidemiology and Public Health, University of Ottawa, Ottawa, Ontario, Canada.",
"Department of Medicine (Hematology), The Ottawa Hospital, Ottawa, Ontario, Canada. Electronic address: [email protected]."
] | [
"39692673"
] | [] | 11.33992 | 5.832326 |
39689708 | 113 | If it is a solid tumor target, then it may be a hematologic cancer target: Bridging the great divide. | Tumor-agnostic US Food and Drug Administration approvals are transforming oncology. They include larotrectinib/entrectinib/repotrectinib (NTRK fusions), selpercatinib (RET fusions), dabrafenib/trametinib (BRAF | [
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10.1038/s41698-024-00701-y | [
"Adashek",
"Munoz",
"Kurzrock"
] | [
"Department of Oncology, The Sidney Kimmel Comprehensive Cancer Center, The Johns Hopkins Hospital, Baltimore, MD, USA. Electronic address: [email protected].",
"Department of Hematology, Mayo Clinic Arizona, Phoenix, AZ, USA. Electronic address: [email protected].",
"Division of Hematology and Oncology, Medical College of Wisconsin, Milwaukee, WI, USA; WIN Consortium, Paris, France; University of Nebraska, Omaha, NE, USA. Electronic address: [email protected]."
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39687729 | 114 | High-affinity chimeric antigen receptor signaling induces an inflammatory program in human regulatory T cells. | Regulatory T cells (Tregs) are promising cellular therapies to induce immune tolerance in organ transplantation and autoimmune disease. The success of chimeric antigen receptor (CAR) T cell therapy for cancer has sparked interest in using CARs to generate antigen-specific Tregs. Here, we compared CAR with endogenous T cell receptor (TCR)/CD28 activation in human Tregs. Strikingly, CAR Tregs displayed increased cytotoxicity and diminished suppression of antigen-presenting cells and effector T (Teff) cells compared with TCR/CD28-activated Tregs. RNA sequencing revealed that CAR Tregs activate Teff cell gene programs. Indeed, CAR Tregs secreted high levels of inflammatory cytokines, with a subset of FOXP3 | [
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"Department of Microbiology and Immunology, Medical University of South Carolina, Charleston, SC, USA.\nDepartment of Regenerative Medicine and Cell Biology, Medical University of South Carolina, Charleston, SC, USA.\nHollings Cancer Center, Medical University of South Carolina, Charleston, SC, USA.",
"Department of Microbiology and Immunology, Medical University of South Carolina, Charleston, SC, USA.\nDepartment of Regenerative Medicine and Cell Biology, Medical University of South Carolina, Charleston, SC, USA.\nHollings Cancer Center, Medical University of South Carolina, Charleston, SC, USA.",
"Bioinformatics Core, Medical University of South Carolina, Charleston, SC, USA.",
"Department of Microbiology and Immunology, Medical University of South Carolina, Charleston, SC, USA.\nDepartment of Regenerative Medicine and Cell Biology, Medical University of South Carolina, Charleston, SC, USA.\nHollings Cancer Center, Medical University of South Carolina, Charleston, SC, USA.",
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"Department of Microbiology and Immunology, Medical University of South Carolina, Charleston, SC, USA.\nDepartment of Regenerative Medicine and Cell Biology, Medical University of South Carolina, Charleston, SC, USA.\nHollings Cancer Center, Medical University of South Carolina, Charleston, SC, USA."
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39687615 | 115 | Hyper-fractionated radiotherapy as a bridging strategy to enhance CAR-T efficacy by regulating T-cell co-stimulatory molecules in relapsed/refractory diffuse large B-cell lymphoma. | Bridging therapy can prevent patients from disease progression while waiting for CAR-T cell preparation. Hyper-fractionated radiotherapy can achieve an effective target dose within a short period, minimize radiation damage, and may modify immune environment compared to conventional radiotherapy.
This study aims to investigate the efficacy and safety of bridging hyper-fractionated radiotherapy in combination with CAR-T therapy for relapsed/refractory diffuse large B-cell lymphoma. The potential mechanisms were explored.
This is a prospective pilot study. After T-cell collection, the patients underwent hyper-fractionated radiotherapy at lesion sites with 1.5 Gy twice daily for 10 days before CAR-T cell infusion. Peripheral blood immune cell subsets and quantitative serum proteomics were assessed before radiotherapy and after radiotherapy before CAR-T cell infusion.
A total of 13 patients have been enrolled. The median follow-up time was 6 (3-24) months after CAR-T infusion. At 3-month follow-up, 9/13(69%) patients had CR, 1/13(8%) patient had PR, 1/13(8%) patient remained SD, and 2/13(15%) patients died of disease progression. The local recurrence rate was 1/13(8%). Seven patients have been followed up for more than 6 months, and they remain in CR. The median PFS and OS were not reached. No grade 3-4 CRS or ICANS were reported. After hyper-fractionated radiotherapy, peripheral PD1+CD8+T/T ratio significantly decreased while quantitative serum proteomics profiling showed a decrease in sCD28.
Hyper-fractionated radiotherapy can rapidly control tumor progression sites without delaying the infusion time. This approach can improve the ORR and does not increase the incidence of CRS and ICANS. The mechanism may be related to the regulation of T-cell co-stimulatory molecules, which demands further exploration. | [
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10.1016/j.radonc.2023.109580 | [
"Ruan",
"Zhou",
"Zhang",
"Zhao",
"Wei",
"Hu",
"Zhang",
"Hou",
"Zhang"
] | [
"Department of Hematology, Peking Union Medical College Hospital, Beijing, China.",
"Department of Hematology, Peking Union Medical College Hospital, Beijing, China.",
"Department of Hematology, Peking Union Medical College Hospital, Beijing, China.",
"Department of Hematology, Peking Union Medical College Hospital, Beijing, China.",
"Department of Hematology, Peking Union Medical College Hospital, Beijing, China.",
"Department of Radiotherapy, Peking Union Medical College Hospital, Beijing, China.",
"Department of Radiotherapy, Peking Union Medical College Hospital, Beijing, China.",
"Department of Radiotherapy, Peking Union Medical College Hospital, Beijing, China.",
"Department of Hematology, Peking Union Medical College Hospital, Beijing, China."
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39684867 | 116 | CAR T Cell Nanosymbionts: Revealing the Boundless Potential of a New Dyad. | Cancer treatment has traditionally focused on eliminating tumor cells but faces challenges such as resistance and toxicity. A promising direction involves targeting the tumor microenvironment using CAR T cell immunotherapy, which has shown potential for treating relapsed and refractory cancers but is limited by high costs, resistance, and toxicity, especially in solid tumors. The integration of nanotechnology into ICAM cell therapy, a concept we have named "CAR T nanosymbiosis", offers new opportunities to overcome these challenges. Nanomaterials can enhance CAR T cell delivery, manufacturing, activity modulation, and targeting of the tumor microenvironment, providing better control and precision. This approach aims to improve the efficacy of CAR T cells against solid tumors, reduce associated toxicities, and ultimately enhance patient outcomes. Several studies have shown promising results, and developing this therapy further is essential for increasing its accessibility and effectiveness. Our "addition by subtraction model" synthesizes these multifaceted elements into a unified strategy to advance cancer treatment paradigms. | [
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10.3389/fpubh.2023.1125577 | [
"Baena",
"Pérez",
"Toro-Pedroza",
"Kitawaki",
"Loukanov"
] | [
"Division of Oncology, Department of Medicine, Fundación Valle del Lili, ICESI University, Carrera 98 No. 18-49, Cali 760032, Colombia.\nLiliCAR-T Group, Fundación Valle del Lili, ICESI University, Cali 760032, Colombia.",
"Division of Oncology, Department of Medicine, Fundación Valle del Lili, ICESI University, Carrera 98 No. 18-49, Cali 760032, Colombia.\nLiliCAR-T Group, Fundación Valle del Lili, ICESI University, Cali 760032, Colombia.",
"Division of Oncology, Department of Medicine, Fundación Valle del Lili, ICESI University, Carrera 98 No. 18-49, Cali 760032, Colombia.\nLiliCAR-T Group, Fundación Valle del Lili, ICESI University, Cali 760032, Colombia.",
"Department of Hematology, Kyoto University Hospital, Kyoto 606-8507, Japan.",
"Department of Chemistry and Materials Science, National Institute of Technology, Gunma College, Maebashi 371-8530, Japan.\nLaboratory of Engineering Nanobiotechnology, University of Mining and Geology \"St. Ivan Rilski\", 1700 Sofia, Bulgaria."
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39682106 | 117 | Advances in Immunotherapy for Endometrial Cancer: Insights into MMR Status and Tumor Microenvironment. | Endometrial cancer is one of the most common gynecological malignancies, and while early-stage cases are highly treatable, recurrent or advanced EC remains challenging to manage. Immunotherapy, particularly immune checkpoint inhibitors, has revolutionized treatment approaches in oncology, and its application in EC has shown promising results. Key to immunotherapy efficacy in EC is the tumor's mismatch repair status, with MMR-deficient tumors demonstrating a higher tumor mutational burden and increased PD-L1 expression, making them more susceptible to immune checkpoint inhibitors (ICIs) such as pembrolizumab, durvalumab, and dostarlimab. However, not all mismatch repair-deficient (MMRd) tumors respond to ICIs, particularly those with a "cold" tumor microenvironment (TME) characterized by poor immune infiltration. In contrast, some MMR-proficient tumors with a "hot" TME respond well to ICIs, underscoring the complex interplay between MMR status, tumor mutational burden (TMB), and TME. To overcome resistance in cold tumors, novel therapies, including Chimeric Antigen Receptor (CAR) T cells and tumor-infiltrating lymphocytes are being explored, offering targeted immune-based strategies to enhance treatment efficacy. This review discusses the current understanding of immunotherapy in EC, emphasizing the prognostic and therapeutic implications of MMR status, TME composition, and emerging cell-based therapies. | [
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10.1038/nature23007 | [
"Albertí-Valls",
"Olave",
"Olomí",
"Macià",
"Eritja"
] | [
"Oncologic Pathology Group, Biomedical Research Institute of Lleida (IRBLleida), University of Lleida (UdL), Av. Rovira Roure 80, 25198 Lleida, Spain.",
"Centro de Investigación Biomédica en Red de Cáncer (CIBERONC), 28029 Madrid, Spain.",
"Developmental and Oncogenic Signaling, Biomedical Research Institute of Lleida (IRBLleida), University of Lleida (UdL), Av. Rovira Roure 80, 25198 Lleida, Spain.",
"Oncologic Pathology Group, Biomedical Research Institute of Lleida (IRBLleida), University of Lleida (UdL), Av. Rovira Roure 80, 25198 Lleida, Spain.",
"Oncologic Pathology Group, Biomedical Research Institute of Lleida (IRBLleida), University of Lleida (UdL), Av. Rovira Roure 80, 25198 Lleida, Spain.\nCentro de Investigación Biomédica en Red de Cáncer (CIBERONC), 28029 Madrid, Spain."
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39682021 | 118 | CAR-based cell therapies for systemic lupus erythematosus. | The remarkable efficacy of chimeric antigen receptor (CAR) T cell therapy in hematological malignancies has provided a solid basis for the therapeutic concept, wherein specific pathogenic cell populations can be eradicated by means of targeted recognition. During the past few years, CAR-based cell therapies have been extensively investigated in preclinical and clinical research across various non-tumor diseases, with particular emphasis in the treatment of autoimmune diseases (ADs), yielding significant advancements. The recent deployment of CD19-directed CAR T cells has induced long-lasting, drug-free remission in patients with systemic lupus erythematosus (SLE) and other systemic AD, alongside a more profound immune reconstruction of B cell repertoire compared with conventional immunosuppressive agents and B cell-targeting biologics. Despite the initial success achieved by CAR T cell therapy, it is critical to acknowledge the divergences in its application between cancer and AD. Through examining recent clinical studies and ongoing research, we highlight the transformative potential of this therapeutic approach in the treatment of SLE, while also addressing the challenges and future directions necessary to enhance the long-term efficacy and safety of CAR-based cell therapies in clinical practice. | [
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10.3389/fimmu.2020.581433 | [
"Wang",
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] | [
"Department of Rheumatology, Shanghai Jiao Tong University School of Medicine Affiliated Renji Hospital, Shanghai 200127, China.",
"Department of Rheumatology, Shanghai Jiao Tong University School of Medicine Affiliated Renji Hospital, Shanghai 200127, China.",
"Department of Rheumatology, Shanghai Jiao Tong University School of Medicine Affiliated Renji Hospital, Shanghai 200127, China.",
"Department of Rheumatology, Shanghai Jiao Tong University School of Medicine Affiliated Renji Hospital, Shanghai 200127, China.\nShanghai Immune Therapy Institute, Shanghai Jiao Tong University School of Medicine Affiliated Renji Hospital, Shanghai 200127, China."
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"39682021"
] | [] | 7.471626 | 4.497714 |
39676854 | 119 | Anti-BCMA and GPRC5D bispecific antibodies in relapsed/refractory primary plasma cell leukemia: a case report. | Plasma cell leukemia (PCL) is an aggressive and high-risk variant of multiple myeloma (MM) with a very poor prognosis. Given its rarity and aggressiveness, there is a lack of clinical trials testing the efficacity of novel therapies in these patients. New immune approaches such as B-cell maturation antigen (BCMA) and G protein-coupled receptor, family C, group 5, member D (GPRC5D) -targeting agents, including chimeric antigen receptor (CAR) T-cells and bispecific antibodies could play a role in PCL treatment. However, PCL patients were excluded from recent pivotal clinical trials testing those agents and only some case reports have been published. We present here the clinical course of a patient with relapsed/refractory (R/R) primary (p) PCL who was treated with anti-BCMA and anti-GPRC5D bispecific antibodies at our center. | [
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"(MM"
] | [
"BCMA",
"GPRC5D",
"bispecific Ab",
"elranatamab",
"plasma cell leukemia (PCL)",
"talquetamab"
] | 0 | 10.3389/fimmu.2024.1495233
10.1038/s41408-021-00587-0
10.1200/JCO.22.02114
10.1038/s41375-021-01431-x
10.1182/blood-2014-03-565051
10.1182/blood-2020-139559
10.1002/ctm2.v11.3
10.3389/fonc.2022.901266
10.1182/blood-2019-125120
10.1016/S1470-2045(16)30206-6
10.1007/s00277-022-05027-y
10.1016/S1470-2045(19)30152-4
10.1038/s41591-023-02528-9
10.1056/NEJMoa2204591 | [
"Bernardi",
"Beauverd",
"Tran",
"Maulini",
"Mappoura",
"Morin",
"Simonetta",
"Cairoli",
"Auner",
"Samii",
"Chalandon",
"de Ramon Ortiz"
] | [
"Division of Haematology, Department of Oncology, Geneva University Hospitals, Geneva, Switzerland.\nTranslational Research Center for Oncohematology, Department of Medicine and Department of Pathology and Immunology, Faculty of Medicine, University of Geneva, Geneva, Switzerland.",
"Division of Haematology, Department of Oncology, Geneva University Hospitals, Geneva, Switzerland.",
"Division of Haematology, Department of Oncology, Geneva University Hospitals, Geneva, Switzerland.",
"Division of Haematology, Department of Oncology, Geneva University Hospitals, Geneva, Switzerland.",
"Division of Haematology, Department of Oncology, Geneva University Hospitals, Geneva, Switzerland.",
"Division of Haematology, Department of Oncology, Geneva University Hospitals, Geneva, Switzerland.",
"Division of Haematology, Department of Oncology, Geneva University Hospitals, Geneva, Switzerland.\nTranslational Research Center for Oncohematology, Department of Medicine and Department of Pathology and Immunology, Faculty of Medicine, University of Geneva, Geneva, Switzerland.",
"Division of Haematology, Department of Oncology, University Hospital of Lausanne (CHUV), Lausanne, Switzerland.",
"Division of Haematology, Department of Oncology, University Hospital of Lausanne (CHUV), Lausanne, Switzerland.",
"Division of Haematology, Department of Oncology, Geneva University Hospitals, Geneva, Switzerland.",
"Division of Haematology, Department of Oncology, Geneva University Hospitals, Geneva, Switzerland.",
"Division of Haematology, Department of Oncology, Geneva University Hospitals, Geneva, Switzerland."
] | [
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] | [] | 4.934918 | 6.13276 |
39674824 | 120 | Evolving strategies for addressing CAR T-cell toxicities. | The field of chimeric antigen receptor (CAR) T-cell therapy has grown from a fully experimental concept to now boasting a multitude of treatments including six FDA-approved products targeting various hematologic malignancies. Yet, along with their efficacy, these therapies come with side effects requiring timely and thoughtful interventions. In this review, we discuss the most common toxicities associated with CAR T-cells to date, highlighting risk factors, prognostication, implications for critical care management, patient experience optimization, and ongoing work in the field of toxicity mitigation. Understanding the current state of the field and standards of practice is critical in order to improve and manage potential toxicities of both current and novel CAR T-cell therapies as they are applied in the clinic. | [
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"potential toxicities",
"critical care management",
"toxicity mitigation",
"patient experience optimization",
"side effects",
"various hematologic malignancies",
"CAR T-cells",
"chimeric antigen receptor",
"ongoing work",
"risk factors",
"CAR) T-cell therapy",
"both current and novel CAR T-cell therapies",
"FDA",
"treatments",
"implications",
"prognostication",
"practice",
"order",
"standards",
"date",
"timely and thoughtful interventions",
"the current state",
"six FDA-approved products",
"these therapies",
"The field",
"the field",
"the most common toxicities",
"a fully experimental concept",
"a multitude",
"their efficacy"
] | [
"B-cell acute lymphoblastic leukemia",
"B-cell lymphoma",
"CAR T-cell",
"Relapse",
"Resistance"
] | 0 | 10.1007/s10555-024-10227-1 | [
"Rankin",
"Duncan",
"Allen",
"Silbert",
"Shah"
] | [
"Pediatric Oncology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, 20892, USA.",
"Pediatric Oncology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, 20892, USA.",
"Division of Hematology, Department of Medicine, Johns Hopkins University, Baltimore, MD, USA.\nDepartment of Critical Care Medicine, National Institutes of Health, Bethesda, MD, USA.",
"Pediatric Oncology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, 20892, USA.",
"Pediatric Oncology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, 20892, USA. [email protected]."
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] | [] | 6.202412 | 4.043425 |
39674638 | 121 | A convenient viral transduction based method for advanced multi-engineering of primary human (CAR) T-cells. | The past decades have illustrated the power of T-cell engineering in the development of new and successful cell therapies, such as chimeric antigen receptor (CAR) T-cells. Despite clinical success in hematological malignancies, it also becomes increasingly clear that additional T-cell engineering will be required to improve efficacy and safety and expand the application to solid tumors. Engineering is most often achieved by viral delivery of transgenes, however, viral vector capacity limitations make efficient and reproducible generation of multi transgene expressing T-cell therapeutics technically challenging. We here describe a convenient and efficient method for the delivery of up to three γ-retroviral CAR vectors in T-cells. We achieved this using virus vector mixtures that are simultaneously produced at high titers by double- or triple- transduced stable virus producer cells. We show that this method is superior in overall efficiency and reproducibility to conventional double or triple CAR transductions, in which separate viral batches are used. Due to its robustness, this method can facilitate the research and the development for advanced T-cell engineering towards more effective and safe therapies. | [
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] | 2024-12-15 | 47 | 39674638 | [
"viral vector capacity limitations",
"viral delivery",
"additional T-cell engineering",
"advanced T-cell engineering",
"Engineering",
"separate viral batches",
"T-cell engineering",
"chimeric antigen receptor",
"T-cell therapeutics",
"new and successful cell therapies",
"hematological malignancies",
"overall efficiency",
"high titers",
"CAR",
"T-cells",
"transgenes",
"this using virus vector mixtures",
"double- or triple- transduced stable virus producer cells",
"conventional double or triple CAR transductions",
"solid tumors",
"clinical success",
"safety",
"CAR) T-cells",
"efficacy",
"reproducibility",
"efficient and reproducible generation",
"up to three γ-retroviral CAR vectors",
"a convenient and efficient method",
"this method",
"more effective and safe therapies"
] | [
"Double",
"Stable and simultaneous virus production",
"T-cell engineering",
"Triple transduction",
"Y-retrovirus"
] | 0 | 10.1016/j.jgeb.2024.100446 | [
"van der Schans",
"Katsarou",
"Kladis",
"Bar",
"Ramirez",
"Themeli",
"Mutis"
] | [
"Department of Hematology, Amsterdam UMC, Location VU University Medical Center, Cancer Center Amsterdam, Room CCA3.38, De Boelelaan 1117, Amsterdam 1081 HV, the Netherlands. Electronic address: [email protected].",
"Department of Hematology, Amsterdam UMC, Location VU University Medical Center, Cancer Center Amsterdam, Room CCA3.38, De Boelelaan 1117, Amsterdam 1081 HV, the Netherlands.",
"Department of Hematology, Amsterdam UMC, Location VU University Medical Center, Cancer Center Amsterdam, Room CCA3.38, De Boelelaan 1117, Amsterdam 1081 HV, the Netherlands.",
"Department of Hematology, Amsterdam UMC, Location VU University Medical Center, Cancer Center Amsterdam, Room CCA3.38, De Boelelaan 1117, Amsterdam 1081 HV, the Netherlands.",
"Department of Hematology, Amsterdam UMC, Location VU University Medical Center, Cancer Center Amsterdam, Room CCA3.38, De Boelelaan 1117, Amsterdam 1081 HV, the Netherlands.",
"Department of Hematology, Amsterdam UMC, Location VU University Medical Center, Cancer Center Amsterdam, Room CCA3.38, De Boelelaan 1117, Amsterdam 1081 HV, the Netherlands.",
"Department of Hematology, Amsterdam UMC, Location VU University Medical Center, Cancer Center Amsterdam, Room CCA3.38, De Boelelaan 1117, Amsterdam 1081 HV, the Netherlands."
] | [
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] | [] | 9.101474 | 2.89545 |
39673975 | 122 | Generation of chimeric antigen receptor-macrophages by using human induced pluripotent stem cells. | Cancer immunotherapy using chimeric antigen receptor (CAR) cells shows high therapeutic efficacy against several types of leukemia. Among acute lymphoblastic leukemias (ALLs), B cell-derived ALL can be cured by CAR-expressing T cells (CAR-Ts); however, CAR-T cells cannot be simply applied for T cell-derived ALL (T-ALL) because antigens expressed by T-ALL cells, but not by CAR-T cells, have not yet been identified. To apply CAR-T therapy for T-ALL, gene editing of CAR-T cells is required to avoid attacking CAR-T cells themselves. Alternatively, CAR-expressing macrophages (CAR-Ms) have proven to be effective against various cancers, suggesting that CAR-Ms may also be effective against T-ALL. Recently, we developed an efficient differentiation induction system to generate a large number of macrophages from human induced pluripotent stem cells (iPSCs). Here, we asked whether these human iPSC-derived macrophages (iPS-MACs) can be used to develop and evaluate CAR-based immunotherapy against T-ALLs. When non-transduced iPS-MACs were co-cultured with human T-ALL-derived cells, the iPS-MACs appeared to phagocytose parts of T-ALL cells; this method of phagocytosis operated mainly through incorporation of small, "bite-sized" vesicles derived from the T-ALL cells into iPS-MACs (similar to trogocytosis). By contrast, when CAR-expressing iPS-MACs were co-cultured with T-ALL cells, iPS-MACs engulfed the whole T-ALL cell. Thus, our differentiation induction system may be a promising tool for building up CAR-M therapy for T-ALLs. | [
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] | 2024-12-15 | 1 | 39673975 | [
"human induced pluripotent stem cells",
"CAR-expressing T cells",
"CAR-T cells",
"CAR",
"T-ALL cells",
"human T-ALL-derived cells",
"ALLs",
"non-transduced iPS-MACs",
"high therapeutic efficacy",
"Cancer immunotherapy",
"CAR-expressing macrophages",
"CAR-T therapy",
"macrophages",
"CAR-expressing iPS-MACs",
"acute lymphoblastic leukemias",
"various cancers",
"iPS-MACs",
"T-ALL",
"several types",
"CAR-M therapy",
"CAR-based immunotherapy",
"B cell-derived ALL",
"antigens",
"T-ALLs",
"leukemia",
"an efficient differentiation induction system",
"CAR-Ms",
"gene editing",
"our differentiation induction system",
"these human iPSC-derived macrophages"
] | [] | 0 | 10.1016/j.bbrc.2024.151158 | [
"Kitajima",
"Hara"
] | [
"Stem Cell Project, Tokyo Metropolitan Institute of Medical Science, Tokyo, Japan. Electronic address: [email protected].",
"Stem Cell Project, Tokyo Metropolitan Institute of Medical Science, Tokyo, Japan; Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo, Japan; Graduate School of Science, Department of Biological Science, Tokyo Metropolitan University, Tokyo, Japan. Electronic address: [email protected]."
] | [
"39673975"
] | [] | 10.296915 | 5.436316 |
39656982 | 123 | [The new generations of CAR-T cells]. | Chimeric antigen receptor (CAR)-T is one of the most promising modern cancer immunotherapies. In the recent years, impressive results have been obtained in the treatment of cancer which led to FDA approval for the treatment of liquid tumors. In this cell-based therapy, immune cells (e.g. T and NK cells) are engineered to express a synthetic receptor CAR to specifically recognize and eliminate cells expressing a target antigen. CAR has evolved through different generations aiming to boost its biological activity and overcome limitations such as low persistence, limited potency, life-threatening toxicity and inefficient activity against solid tumor. The present review provides an overview of the different CAR generations, starting from the 1
Les nouvelles générations de cellules CAR-T.
L’approche CAR-T, qui consiste à utiliser des lymphocytes T exprimant un récepteur de l’antigène recombinant (CAR, pour chimeric antigen receptor) permettant d’éliminer les cellules présentant un antigène particulier, est l’une des immunothérapies les plus prometteuses pour soigner les cancers. L’ingénierie des CAR-T a évolué au fil de leurs générations, pour renforcer leur activité et leur spécificité, et surmonter leurs limites, comme leur faible persistance, leur toxicité et leur inefficacité dans la lutte contre les tumeurs solides. Cette revue explore les différentes générations de CAR, les tests cliniques en cours sur le cancer et les maladies auto-immunes, ainsi que les limites associées aux cellules CAR-T dans le traitement des cancers. | [
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] | 2024-12-15 | 1 | 39656982 | [
"CAR",
"pour chimeric antigen receptor",
"toxicité et leur inefficacité dans la lutte",
"et leur spécificité",
"T exprimant",
"pour renforcer leur activité",
"et surmonter leurs limites",
"un récepteur de l’antigène recombinant",
"Chimeric antigen receptor",
"la lutte contre les tumeurs solides",
"permettant d’éliminer les cellules",
"different generations",
"à utiliser des",
"L’ingénierie des CAR-T",
"des cancers",
"comme leur faible persistance",
"immune cells",
"inefficient activity",
"CAR-T dans",
"leur spécificité",
"cancer",
"L’approche CAR-T",
"un antigène",
"comme leur",
"leur toxicité",
"cells",
"a synthetic receptor CAR",
"limited potency",
"impressive results",
"low persistence"
] | [] | 0 | 10.1051/medsci/2024151 | [
"Messaoudi",
"Perez",
"Gouveia"
] | [
"Dynamics of intracellular organization laboratory, Institut Curie, PSL Research University, Sorbonne Université, CNRS, UMR144, Paris, France.",
"Dynamics of intracellular organization laboratory, Institut Curie, PSL Research University, Sorbonne Université, CNRS, UMR144, Paris, France.",
"Dynamics of intracellular organization laboratory, Institut Curie, PSL Research University, Sorbonne Université, CNRS, UMR144, Paris, France - Cell therapy Acceleration and Innovation (CellAction), Institut Curie, Suresnes, France."
] | [
"39656982"
] | [] | 9.394945 | 3.920642 |
39673705 | 124 | Protocol for the development of a bioluminescent AML-PDX mouse model for the evaluation of CAR T cell therapy. | Patient-derived xenograft (PDX) models of acute myeloid leukemia (AML-PDX) offer advantages over cell line models by capturing the complexity and heterogeneity of patient-derived samples. Here, we present a protocol for developing a bioluminescent AML-PDX model in mice to evaluate chimeric antigen receptor (CAR) T cell therapy. We describe steps for transducing, engrafting, expanding, and enriching AML-PDX cells. We then detail procedures for in vitro and in vivo validation of the AML-PDX model for the evaluation of CAR T cell immunotherapy. For complete details on the use and execution of this protocol, please refer to Caulier et al. | [
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] | [
"cancer",
"cell biology",
"cell culture",
"flow cytometry",
"immunology",
"model organisms",
"molecular biology"
] | 0 | 10.1016/j.xpro.2024.103522
10.1016/j.xcrm.2024.101572
10.3389/fimmu.2021.648580
10.1038/s41571-022-00721-2
10.3390/cancers15112989
10.1186/s12967-022-03405-8
10.1038/s41392-023-01419-2
10.1158/2159-8290.CD-14-0001
10.1038/s41571-022-00682-6
10.1016/j.ccell.2020.03.007
10.1158/1078-0432.CCR-16-2392
10.1007/978-1-0716-2453-1_24
10.1371/journal.pone.0052798
10.1186/s42826-020-00045-1 | [
"Safont",
"Leitch",
"Popa",
"Gjerstad",
"Caulier",
"Inderberg",
"Wälchli",
"Gelebart",
"Cormack"
] | [
"Precision Oncology Research Group, University of Bergen, Bergen, Norway; Department of Clinical Science, University of Bergen, Bergen, Norway; Kinn Therapeutics, Bergen, Norway. Electronic address: [email protected].",
"Precision Oncology Research Group, University of Bergen, Bergen, Norway; Department of Clinical Science, University of Bergen, Bergen, Norway; Centre for Cancer Biomarkers (CCBIO), University of Bergen, Bergen, Norway.",
"Precision Oncology Research Group, University of Bergen, Bergen, Norway; Department of Clinical Science, University of Bergen, Bergen, Norway; Kinn Therapeutics, Bergen, Norway.",
"Precision Oncology Research Group, University of Bergen, Bergen, Norway; Department of Clinical Science, University of Bergen, Bergen, Norway.",
"Translational Research Unit, Section for Cellular Therapy, Department of Oncology, Oslo University Hospital, Oslo, Norway.",
"Translational Research Unit, Section for Cellular Therapy, Department of Oncology, Oslo University Hospital, Oslo, Norway.",
"Translational Research Unit, Section for Cellular Therapy, Department of Oncology, Oslo University Hospital, Oslo, Norway.",
"Precision Oncology Research Group, University of Bergen, Bergen, Norway; Department of Clinical Science, University of Bergen, Bergen, Norway; Department of Hematology, Haukeland University Hospital, Bergen, Norway; Centre for Cancer Biomarkers (CCBIO), University of Bergen, Bergen, Norway.",
"Precision Oncology Research Group, University of Bergen, Bergen, Norway; Department of Clinical Science, University of Bergen, Bergen, Norway; Department of Hematology, Haukeland University Hospital, Bergen, Norway; Centre for Pharmacy, Department of Clinical Science, University of Bergen, Bergen, Norway; Centre for Cancer Biomarkers (CCBIO), University of Bergen, Bergen, Norway. Electronic address: [email protected]."
] | [
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39673125 | 125 | Tailoring capsid-directed evolution technology for improved AAV-mediated CAR-T generation. | Chimeric antigen receptor (CAR) T cell (CAR-T) therapies present options for patients diagnosed with certain leukemias. Recent advances of the technology included a method to integrate the CAR into the T cell receptor alpha constant (TRAC) locus to take advantage of the endogenous promoter and regulatory elements for CAR expression. This method used adeno-associated viral (AAV) vectors based on AAV6 to deliver the donor template encoding the CAR construct. Since the original publication, improvements have been made to this targeted CAR integration technique; however, none of those techniques focused on improving the AAV vector used to deliver the therapeutic cargo. The herein presented study developed a novel AAV capsid directed evolution platform that allows for specifically selecting for novel AAV capsid variants that enable more efficient targeted gene editing-mediated CAR construct integration into the TRAC locus in primary T cells. Using this new platform, we selected several novel AAVs that enable more efficient editing in T cells than AAV6. Two novel capsids, AAV-T1 and AAV-T2, were able to mediate 5-fold improvement for on-target knockin, which resulted in 5-fold reduction of the vector dose to produce highly cytolytic T cells against a brain tumor cell line. | [
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] | 2024-12-14 | 1 | 39673125 | [
"novel AAV capsid variants",
"AAV",
"CAR expression",
"CAR",
"several novel AAVs",
"present options",
"Chimeric antigen receptor",
"primary T cells",
"this targeted CAR integration technique",
"regulatory elements",
"the AAV vector",
"integration",
"T cells",
"improvements",
"more efficient targeted gene editing-mediated CAR",
"a novel AAV capsid directed evolution platform",
"certain leukemias",
"a brain tumor cell line",
"Recent advances",
"AAV-T2",
"AAV-T1",
"AAV6",
"5-fold improvement",
"CAR) T cell",
"patients",
"highly cytolytic T cells",
"5-fold reduction",
"AAV-T1 and AAV-T2",
"advantage",
"the T cell receptor alpha constant (TRAC) locus"
] | [
"AAV",
"CAR-T",
"T-cell engineering",
"cancer",
"cancer gene therapy",
"cell therapy",
"directed evolution",
"gene therapy",
"high-grade glioma",
"synthetic biology"
] | 0 | 10.1016/j.ymthe.2024.12.012 | [
"Westhaus",
"Barba-Sarasua",
"Chen",
"Hsu",
"Scott",
"Knight",
"Haase",
"Mesa Mora",
"Houghton",
"Roca-Pinilla",
"Kalajdzic",
"O'Neill",
"Thrasher",
"Santilli",
"Lisowski"
] | [
"Translational Vectorology Research Unit, Children's Medical Research Institute, Faculty of Medicine and Health, The University of Sydney, Westmead, NSW, Australia; Infection, Immunity and Inflammation Research and Teaching Department, Great Ormond Street Institute of Child Health, University College, London, UK.",
"Translational Vectorology Research Unit, Children's Medical Research Institute, Faculty of Medicine and Health, The University of Sydney, Westmead, NSW, Australia.",
"Children's Cancer Research Unit, Kids Research, The Children's Hospital at Westmead, Faculty of Medicine and Health, The University of Sydney, Westmead, NSW, Australia.",
"Children's Cancer Research Unit, Kids Research, The Children's Hospital at Westmead, Faculty of Medicine and Health, The University of Sydney, Westmead, NSW, Australia.",
"Translational Vectorology Research Unit, Children's Medical Research Institute, Faculty of Medicine and Health, The University of Sydney, Westmead, NSW, Australia; Australian e-Health Research Centre, Commonwealth Scientific and Industrial Research Organisation, Sydney, NSW, Australia.",
"Translational Vectorology Research Unit, Children's Medical Research Institute, Faculty of Medicine and Health, The University of Sydney, Westmead, NSW, Australia.",
"Translational Vectorology Research Unit, Children's Medical Research Institute, Faculty of Medicine and Health, The University of Sydney, Westmead, NSW, Australia.",
"Translational Vectorology Research Unit, Children's Medical Research Institute, Faculty of Medicine and Health, The University of Sydney, Westmead, NSW, Australia.",
"Infection, Immunity and Inflammation Research and Teaching Department, Great Ormond Street Institute of Child Health, University College, London, UK.",
"Translational Vectorology Research Unit, Children's Medical Research Institute, Faculty of Medicine and Health, The University of Sydney, Westmead, NSW, Australia.",
"Vector and Genome Engineering Facility, Children's Medical Research Institute, Faculty of Medicine and Health, The University of Sydney, Westmead, NSW, Australia.",
"Children's Cancer Research Unit, Kids Research, The Children's Hospital at Westmead, Faculty of Medicine and Health, The University of Sydney, Westmead, NSW, Australia.",
"Infection, Immunity and Inflammation Research and Teaching Department, Great Ormond Street Institute of Child Health, University College, London, UK.",
"Infection, Immunity and Inflammation Research and Teaching Department, Great Ormond Street Institute of Child Health, University College, London, UK.",
"Translational Vectorology Research Unit, Children's Medical Research Institute, Faculty of Medicine and Health, The University of Sydney, Westmead, NSW, Australia; Australian Genome Therapeutics Centre, Children's Medical Research Institute and Sydney Children's Hospitals Network, Westmead, NSW 2145, Australia; Laboratory of Molecular Oncology and Innovative Therapies, Military Institute of Medicine - National Research Institute, Warsaw, Poland. Electronic address: [email protected]."
] | [
"39673125"
] | [] | 9.205066 | 2.89508 |
39672954 | 126 | Targeting peptide antigens using a multiallelic MHC I-binding system. | Identifying highly specific T cell receptors (TCRs) or antibodies against epitopic peptides presented by class I major histocompatibility complex (MHC I) proteins remains a bottleneck in the development of targeted therapeutics. Here, we introduce targeted recognition of antigen-MHC complex reporter for MHC I (TRACeR-I), a generalizable platform for targeting peptides on polymorphic HLA-A*, HLA-B* and HLA-C* allotypes while overcoming the cross-reactivity challenges of TCRs. Our TRACeR-MHC I co-crystal structure reveals a unique antigen recognition mechanism, with TRACeR forming extensive contacts across the entire peptide length to confer single-residue specificity at the accessible positions. We demonstrate rapid screening of TRACeR-I against a panel of disease-relevant HLAs with peptides derived from human viruses (human immunodeficiency virus, Epstein-Barr virus and severe acute respiratory syndrome coronavirus 2), and oncoproteins (Kirsten rat sarcoma virus, paired-like homeobox 2b and New York esophageal squamous cell carcinoma 1). TRACeR-based bispecific T cell engagers and chimeric antigen receptor T cells exhibit on-target killing of tumor cells with high efficacy in the low nanomolar range. Our platform empowers the development of broadly applicable MHC I-targeting molecules for research, diagnostic and therapeutic applications. | [
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"Department of Chemistry, Stanford University, Stanford, CA, USA.",
"Center for Computational and Genomic Medicine, Department of Pathology and Laboratory Medicine, Children's Hospital of Philadelphia, Philadelphia, PA, USA.\nDepartment of Biochemistry and Biophysics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.",
"Center for Computational and Genomic Medicine, Department of Pathology and Laboratory Medicine, Children's Hospital of Philadelphia, Philadelphia, PA, USA.\nDepartment of Biochemistry and Biophysics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.",
"Center for Computational and Genomic Medicine, Department of Pathology and Laboratory Medicine, Children's Hospital of Philadelphia, Philadelphia, PA, USA.\nDepartment of Biochemistry and Biophysics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.",
"Department of Immunology and Microbiology, Scripps Research Institute, La Jolla, CA, USA.",
"Department of Bioengineering, Stanford University, Stanford, CA, USA.\nDepartment of Genetics, Stanford University, Stanford, CA, USA.",
"Center for Computational and Genomic Medicine, Department of Pathology and Laboratory Medicine, Children's Hospital of Philadelphia, Philadelphia, PA, USA.\nCancer Biology Graduate Group, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.",
"Department of Radiation Oncology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.",
"Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.",
"Center for Computational and Genomic Medicine, Department of Pathology and Laboratory Medicine, Children's Hospital of Philadelphia, Philadelphia, PA, USA.\nDepartment of Biochemistry and Biophysics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.",
"Center for Computational and Genomic Medicine, Department of Pathology and Laboratory Medicine, Children's Hospital of Philadelphia, Philadelphia, PA, USA.\nDepartment of Biochemistry and Biophysics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.",
"Department of Chemical Engineering, Stanford University, Stanford, CA, USA.",
"Department of Bioengineering, Stanford University, Stanford, CA, USA.",
"Department of Bioengineering, Stanford University, Stanford, CA, USA.",
"Department of Radiation Oncology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.",
"Department of Bioengineering, Stanford University, Stanford, CA, USA.",
"Department of Chemistry, Stanford University, Stanford, CA, USA.",
"Department of Bioengineering, Stanford University, Stanford, CA, USA.",
"Center for Computational and Genomic Medicine, Department of Pathology and Laboratory Medicine, Children's Hospital of Philadelphia, Philadelphia, PA, USA.\nDepartment of Biochemistry and Biophysics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.",
"Center for Computational and Genomic Medicine, Department of Pathology and Laboratory Medicine, Children's Hospital of Philadelphia, Philadelphia, PA, USA.\nDepartment of Biochemistry and Biophysics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.",
"Department of Immunology and Microbiology, Scripps Research Institute, La Jolla, CA, USA.",
"Biophysics Program, Stanford University, Stanford, CA, USA.",
"Center for Computational and Genomic Medicine, Department of Pathology and Laboratory Medicine, Children's Hospital of Philadelphia, Philadelphia, PA, USA.\nDepartment of Biochemistry and Biophysics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.",
"Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.",
"Department of Radiation Oncology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.",
"Department of Bioengineering, Stanford University, Stanford, CA, USA.\nDepartment of Genetics, Stanford University, Stanford, CA, USA.\nStanford Cancer Institute, Stanford University, Stanford, CA, USA.\nChan-Zuckerberg Biohub, San Francisco, CA, USA.",
"Department of Immunology and Microbiology, Scripps Research Institute, La Jolla, CA, USA.",
"Center for Computational and Genomic Medicine, Department of Pathology and Laboratory Medicine, Children's Hospital of Philadelphia, Philadelphia, PA, USA. [email protected].\nDepartment of Biochemistry and Biophysics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA. [email protected].",
"Department of Chemistry, Stanford University, Stanford, CA, USA. [email protected].\nDepartment of Bioengineering, Stanford University, Stanford, CA, USA. [email protected].\nBiophysics Program, Stanford University, Stanford, CA, USA. [email protected]."
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] | [] | 9.2502 | 4.917755 |
39672646 | 127 | The Role of Radiotherapy in Lymphoma Patients Undergoing CAR T Therapy: Past, Present, and Future. | Chimeric antigen receptor (CAR) T-cell receptor therapy has transformed outcomes for patients with relapsed and refractory diffuse large B-cell lymphoma (R/R DLBCL). It is currently approved in the third line for all patients and in the second line for early relapsed or primary refractory disease. Although CAR T cell therapy offers the potential for improved outcomes, its use may also include logistical delays related to referral, medical, social, and financial clearance as well as manufacturing time; more than half of patients experience disease recurrence or progression while awaiting CAR T infusion. Bridging radiotherapy, defined as radiation delivered between the decision to pursue CAR T and infusion of CAR T cells, has become an attractive option for patients who would benefit from local disease control or palliation of symptoms. Additionally, patterns of failure analyses have revealed a dominant role of local disease progression, which has fueled investigations on bridging and early salvage radiation to improve long-term outcomes in patients, particularly those with localized or high-risk disease. Several potential mechanisms by which radiation therapy may improve CAR T efficacy have been proposed that include cytoreduction, tumor debulking, neutralization of immunosuppressive hypoxic and acidic tumor microenvironments, and immunologic and pro-apoptotic synergy between radiation and CAR T. Prospective clinical trials and translational work are ongoing and are needed to inform our conceptual understanding of potential mechanisms by which radiation therapy may improve CAR T efficacy and toxicity, identify which patients may be most likely to benefit, and confirm proposed clinical benefits. | [
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] | 2024-12-14 | 1 | 39672646 | [
"CAR T cell therapy",
"CAR T cells",
"CAR T efficacy",
"CAR T",
"local disease progression",
"patients",
"local disease control",
"early salvage radiation",
"CAR T infusion",
"CAR T. Prospective clinical trials",
"radiation",
"experience disease recurrence",
"improved outcomes",
"acidic tumor microenvironments",
"proposed clinical benefits",
"potential mechanisms",
"Several potential mechanisms",
"pro-apoptotic synergy",
"tumor debulking",
"outcomes",
"manufacturing time",
"Chimeric antigen receptor",
"translational work",
"logistical delays",
"immunosuppressive hypoxic",
"failure analyses",
"progression",
"which radiation therapy",
"CAR) T-cell receptor therapy",
"large B-cell lymphoma"
] | [] | 0 | 10.1016/j.semradonc.2024.10.005 | [
"Wallington",
"Imber",
"Scordo",
"Robinson"
] | [
"Department of Therapeutic Radiology, Yale Cancer Center, New Haven, CT.",
"Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, New York, NY.",
"Department of Medicine, Adult Bone Marrow Transplant Service, Memorial Sloan Kettering Cancer Center, New York, NY; Department of Medicine, Weill Cornell Medical College, New York, NY.",
"Department of Therapeutic Radiology, Yale Cancer Center, New Haven, CT. Electronic address: [email protected]."
] | [
"39672646"
] | [] | 6.462418 | 5.359347 |
39670821 | 128 | Advances in CD19-targeting CAR-T cell therapies for multiple myeloma. | Emerging evidence suggests that, while CD19 is primarily expressed on immature B-cell precursors, it is also present on drug-resistant plasma cells that have been postulated to function as multiple myeloma (MM) stem cells, driving the progression of relapsing disease. Targeting CD19 with chimeric antigen receptor (CAR) T cells offers a promising strategy for addressing this residual disease burden, potentially leading to more durable treatments and enhanced relapse prevention.
This review examines the molecular basis of CD19-targeted CAR-T therapy in MM, highlighting its potential, key challenges, and efficacy and safety in early clinical trials for relapsed/refractory and newly diagnosed MM.
CD19 expression in MM correlates with poor prognosis and may be significantly underestimated, particularly following debulking therapy, as demonstrated by advanced visualization technologies like single molecule-sensitive direct stochastic optical reconstruction microscopy (dSTORM). Early-phase trials using CD19-directed CAR-T as post-transplant consolidation show promise in prolonging progression-free survival. Multi-target approaches, e.g. the bispecific BCMA×CD19 CAR-T product GC012F, are advancing through clinical development with encouraging safety and efficacy data. However, randomized controlled trials will be necessary to confirm the role and positioning of CD19-directed CAR-T cells within the current MM treatment landscape. | [
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] | 2024-12-13 | 1 | 39670821 | [
"CD19 expression",
"CD19",
"early clinical trials",
"MM",
"post-transplant consolidation show promise",
"randomized controlled trials",
"Multi-target approaches",
"relapsing disease",
"debulking therapy",
"CAR",
"advanced visualization technologies",
"clinical development",
"CD19-directed CAR-T cells",
"enhanced relapse prevention",
"poor prognosis",
"immature B-cell precursors",
"drug-resistant plasma cells",
"CD19-targeted CAR-T therapy",
"the current MM treatment landscape",
"key challenges",
"multiple myeloma (MM) stem cells",
"efficacy",
"safety",
"CD19-directed CAR-T",
"Emerging evidence",
"the bispecific BCMA×CD19 CAR-T product",
"Early-phase trials",
"positioning",
"this residual disease burden",
"safety and efficacy data"
] | [
"B-cell maturation antigen",
"CD19",
"Multiple myeloma",
"chimeric antigen receptor (CAR) T cells",
"dSTORM",
"myeloma stem cell",
"ultra-resolution microscopy"
] | 0 | 10.1080/14712598.2024.2443093 | [
"Steinhardt",
"Einsele",
"Waldschmidt"
] | [
"Department of Internal Medicine II, University Hospital of Würzburg, Würzburg, Germany.",
"Department of Internal Medicine II, University Hospital of Würzburg, Würzburg, Germany.",
"Department of Internal Medicine II, University Hospital of Würzburg, Würzburg, Germany."
] | [
"39670821"
] | [] | 4.864729 | 6.154087 |
39668521 | 129 | Chimeric antigen receptor copies in cell-free DNA predict relapse in aggressive B-cell lymphoma patients treated with CAR T-cell therapy. | Chimeric antigen receptor (CAR) T-cell therapy has emerged as a transformative treatment for aggressive B-cell lymphomas (ABCL), However, about half of patients relapse, most of them early. This study investigates the detection of CAR copies in circulating cell-free DNA (cfDNA) as a potential predictive biomarker of early relapse (<6 months) to improve patient management. In this research, we have consecutively selected 73 ABCL patients treated with anti-CD19 CAR T-cells, analysing CAR levels in peripheral blood and other clinical variables. Our results indicate that no correlation is present between genomic DNA and cfDNA; moreover, higher levels of CAR-cfDNA on day +14 after infusion (0.44 vs. 0.07; p = 0.019) are associated with improved 6-month progression-free survival rates (74.2% vs. 26%. p < 0.01), suggesting that CAR-cfDNA could be a strong predictor of CAR T-cell therapy short-term outcomes. These findings underscore the potential of integrating CAR-cfDNA analysis into routine clinical practice to enhance the prognostic accuracy and therapeutic strategies for ABCL patients undergoing CAR T-cell therapy. | [
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] | 2024-12-13 | 1 | 39668521 | [
"ABCL patients",
"CAR levels",
"CAR T-cell therapy",
"cfDNA",
"CAR copies",
"routine clinical practice",
"anti-CD19 CAR T-cells",
"patients",
"ABCL",
"other clinical variables",
"CAR T-cell therapy short-term outcomes",
"CAR",
"CAR-cfDNA analysis",
"genomic DNA",
"CAR) T-cell therapy",
"aggressive B-cell lymphomas",
"cell-free DNA",
"early relapse",
"peripheral blood",
"CAR-cfDNA",
"therapeutic strategies",
"Chimeric antigen receptor",
"73 ABCL patients",
"patient management",
"p",
"infusion",
"day",
"lymphomas",
"improved 6-month progression-free survival rates",
"a potential predictive biomarker"
] | [
"CAR T‐cells",
"cfDNA",
"digital PCR",
"lymphoma",
"relapse"
] | 0 | 10.1111/bjh.19916 | [
"de la Iglesia-San Sebastián",
"López-Esteban",
"Bastos-Oreiro",
"Fernández de Córdoba-Oñate",
"Gutierrez",
"Carbonell",
"Bailén",
"Gómez-Centurión",
"Fernández-Caldas",
"Castilla",
"Anguita",
"Kwon",
"García-Sanz",
"Buño",
"Martínez-Laperche"
] | [
"Department of Hematology, Hospital General Universitario Gregorio Marañón, Madrid, Spain.\nHealth Research Institute Gregorio Marañón, Madrid, Spain.\nDoctorate School, Autonomous University of Madrid, Madrid, Spain.",
"Department of Hematology, Hospital General Universitario Gregorio Marañón, Madrid, Spain.\nHealth Research Institute Gregorio Marañón, Madrid, Spain.",
"Department of Hematology, Hospital General Universitario Gregorio Marañón, Madrid, Spain.\nHealth Research Institute Gregorio Marañón, Madrid, Spain.",
"Department of Hematology, Hospital General Universitario Gregorio Marañón, Madrid, Spain.\nHealth Research Institute Gregorio Marañón, Madrid, Spain.",
"Department of Hematology, Hospital General Universitario Gregorio Marañón, Madrid, Spain.\nHealth Research Institute Gregorio Marañón, Madrid, Spain.",
"Department of Hematology, Hospital General Universitario Gregorio Marañón, Madrid, Spain.\nHealth Research Institute Gregorio Marañón, Madrid, Spain.",
"Department of Hematology, Hospital General Universitario Gregorio Marañón, Madrid, Spain.\nHealth Research Institute Gregorio Marañón, Madrid, Spain.",
"Department of Hematology, Hospital General Universitario Gregorio Marañón, Madrid, Spain.\nHealth Research Institute Gregorio Marañón, Madrid, Spain.",
"Department of Hematology, Hospital General Universitario Gregorio Marañón, Madrid, Spain.\nHealth Research Institute Gregorio Marañón, Madrid, Spain.",
"Department of Hematology, Hospital General Universitario Gregorio Marañón, Madrid, Spain.\nHealth Research Institute Gregorio Marañón, Madrid, Spain.",
"Department of Hematology, Hospital General Universitario Gregorio Marañón, Madrid, Spain.\nHealth Research Institute Gregorio Marañón, Madrid, Spain.",
"Department of Hematology, Hospital General Universitario Gregorio Marañón, Madrid, Spain.\nHealth Research Institute Gregorio Marañón, Madrid, Spain.",
"Department of Hematology, Hospital General Universitario Gregorio Marañón, Madrid, Spain.\nHealth Research Institute Gregorio Marañón, Madrid, Spain.",
"Department of Hematology, Hospital General Universitario Gregorio Marañón, Madrid, Spain.\nHealth Research Institute Gregorio Marañón, Madrid, Spain.\nDepartment of Cell Biology, Complutense University of Madrid, Madrid, Spain.\nGenomics Unit, Hospital General Universitario Gregorio Marañón, Health Research Institute Gregorio Marañón, Madrid, Spain.",
"Department of Hematology, Hospital General Universitario Gregorio Marañón, Madrid, Spain.\nHealth Research Institute Gregorio Marañón, Madrid, Spain."
] | [
"39668521"
] | [] | 6.194345 | 5.23348 |
39667756 | 130 | Clinical trials, challenges, and changes in TCR-based therapeutics for hematologic malignancies. | T cells engineered to express antigen-specific T cell receptors (TCR; TCR-T) are a promising class of immunotherapeutic for patients with hematologic malignancies. Like chimeric antigen receptor-engineered T cells (CAR-T), TCR-T are cell products with defined specificity and composition. Unlike CAR-T, TCR-T can recognize targets arising both from intracellular and cell surface proteins and leverage the sensitivity of natural TCR signaling machinery. A growing number of TCR-T targeting various antigens in different hematologic malignancies are in early-phase clinical trials, and more are in preclinical development.
This review covers results from early-phase TCR-T clinical trials for hematologic malignancies. Challenges in the field are reviewed, including identifying optimal targets, engaging CD4
In the future, TCR-T's promise for hematologic malignancies will be borne out in later-phase clinical trials and approvals for clinical use. Improved antigen discovery methods will help build the toolbox of targets needed for broadly applicable TCR-T. Rationally designed TCR-T modifications including incorporation of accessory receptors and gene editing will enhance TCR-T function. New hybrid receptors combining features of TCR and CAR will enter the clinic. | [
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] | 2024-12-13 | 1 | 39667756 | [
"TCR",
"T cells",
"hematologic malignancies",
"cell products",
"accessory receptors",
"TCR-T modifications",
"TCR-T function",
"New hybrid receptors",
"optimal targets",
"different hematologic malignancies",
"early-phase TCR-T clinical trials",
"Improved antigen discovery methods",
"TCR-T",
"chimeric antigen receptor-engineered T cells",
"various antigens",
"targets",
"clinical use",
"antigen-specific T cell receptors",
"early-phase clinical trials",
"natural TCR",
"later-phase clinical trials",
"TCR-Ts promise",
"CAR-T",
"gene editing",
"intracellular and cell surface proteins",
"defined specificity",
"CAR",
"preclinical development",
"broadly applicable TCR-T.",
"features"
] | [
"T cell immunotherapy",
"engineered T cell receptor",
"hematologic malignancies",
"leukemia",
"tumor-associated antigen"
] | 0 | 10.1080/17474086.2024.2441962 | [
"Biernacki",
"Bleakley"
] | [
"Clinical Research Division, Fred Hutchinson Cancer Center, Seattle, WA, USA.",
"Clinical Research Division, Fred Hutchinson Cancer Center, Seattle, WA, USA.\nDepartment of Pediatrics, University of Washington, Seattle, WA, USA."
] | [
"39667756"
] | [] | 9.386854 | 4.384928 |
39667221 | 131 | Advancing the next generation of cancer treatment with circular RNAs in CAR-T cell therapy. | Chimeric Antigen Receptor T-cell (CAR-T) therapy has revolutionized the treatment of hematological malignancies. However, its effectiveness against solid tumors remains constrained by challenges such as T-cell exhaustion, limited persistence, and off-target effects. These challenges highlight critical gaps in current CAR-T cell therapeutic strategies, particularly for solid tumor applications. Circular RNAs (circRNAs) represent a transformative class of non-coding RNAs, known for their exceptional stability and precise regulatory functions, positioning them as promising candidates for enhancing next-generation CAR-T cell therapies. Notably, circRNAs can bridge the gap between preclinical research and clinical application by offering innovative solutions to overcome technical hurdles and improve therapeutic outcomes. Despite their potential, circRNAs remain underexplored in clinical application of CAR-T cell therapies for solid tumors, presenting a significant opportunity for innovation. The mechanisms through which circRNAs modulate CAR-T cell exhaustion, persistence, and tumor specificity are not yet fully understood, and technical challenges, such as achieving efficient and targeted circRNA delivery, which still need to be addressed. This review highlights the importance of integrating circRNAs into CAR-T cell therapy to enhance specificity, minimize off-target effects, and improve therapeutic durability. By emphasizing the innovative potential of circRNAs and identifying key research gaps, this review provides a roadmap for advancing CAR-T cell therapy and setting the stage for the next generation of personalized cancer treatments. | [
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] | 2024-12-13 | 1 | 39667221 | [
"solid tumor applications",
"CAR-T cell therapies",
"CAR-T cell therapy",
"solid tumors",
"current CAR-T cell therapeutic strategies",
"CAR-T cell exhaustion",
"tumor specificity",
"non-coding RNAs",
"key research gaps",
"technical challenges",
"clinical application",
"circRNAs",
"T-cell exhaustion",
"next-generation CAR-T cell therapies",
"precise regulatory functions",
"critical gaps",
"Circular RNAs",
"technical hurdles",
"therapeutic outcomes",
"therapeutic durability",
"personalized cancer treatments",
"preclinical research",
"innovative solutions",
"circRNA delivery",
"challenges",
"limited persistence",
"specificity",
"persistence",
"Chimeric Antigen Receptor T-cell (CAR-T) therapy",
"target"
] | [
"CAR-T cell therapy",
"Cancer immunotherapy",
"Circular RNAs (circRNAs)",
"Gene editing",
"T-cell exhaustion",
"Tumor microenvironment (TME)"
] | 0 | 10.1016/j.biopha.2024.117753 | [
"Huang",
"Xu",
"Baran",
"Ma"
] | [
"Department of Hepatobiliary and Pancreatic Surgery, The First People's Hospital of Huzhou, The First Affiliated Hospital of Huzhou University, Huzhou, Zhejiang 313000, China. Electronic address: [email protected].",
"Department of Surgical Teaching and Research, Huzhou University School of Medicine, Huzhou, Zhejiang 313000, China. Electronic address: [email protected].",
"Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA; Department of Experimental Hematology, Institute of Hematology and Transfusion Medicine, Warsaw 00-791, Poland. Electronic address: [email protected].",
"Department of Medicine, Sanford Stem Cell Institute, Moores Cancer Center, University of California San Diego, La Jolla, CA 92093, USA. Electronic address: [email protected]."
] | [
"39667221"
] | [] | 9.24067 | 4.209198 |
39664387 | 132 | Hypoimmunogenic CD19 CAR-NK cells derived from embryonic stem cells suppress the progression of human B-cell malignancies in xenograft animals. | Chimeric antigen receptor (CAR) engineered natural killer (NK) cells exhibit advantages such as MHC-independent recognition and strong anti-tumor functions. However, allogeneic CAR-NK cells derived from human tissues are heterogeneous and susceptible to clearance by hosts.
We generated a B2M knockout, HLA-E and CD19 CAR ectopic expressing embryonic stem cell (ESC) line, which differentiated normally and gave rise to homogeneous CD19 CAR-NK (CD19 CAR-UiNK) cells using an organoid aggregate induction method. The CD19 CAR-UiNK were co-cultured with T cells or NK cells derived from peripheral blood mononuclear cells (PBMC) with the mismatched HLA to evaluate the immunogenicity of CD19 CAR-UiNK cells. We further assessed the therapeutic effects of CD19 CAR-UiNK cells on CD19
The CD19 CAR-UiNK cells exhibited typical expression patterns of activating and inhibitory receptors, and crucial effector molecules of NK cells, similar to those of unmodified NK cells. In co-culture assays, the CD19 CAR-UiNK cells evaded allogeneic T cell response and suppressed allogeneic NK cell response. Functionally, the CD19 CAR-UiNK cells robustly secreted IFN-γ and TNF-α, and upregulated CD107a upon stimulation with Nalm-6 tumor cells. The CD19 CAR-UiNK cells effectively eliminated CD19
We offer a strategy for deriving homogeneous and hypoimmunogenic CD19 CAR-iNK cells with robust anti-tumor effects from ESCs. Our study has significant implications for developing hypoimmunogenic CD19 CAR-NK cell therapy using human ESC as an unlimited cell source. | [
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39664377 | 133 | c-MET and the immunological landscape of cancer: novel therapeutic strategies for enhanced anti-tumor immunity. | Cellular mesenchymal-epithelial transition factor (c-MET), also known as hepatocyte growth factor receptor (HGFR), is a crucial receptor tyrosine kinase implicated in various solid tumors, including lung, breast, and liver cancers. The concomitant expression of c-MET and PD-L1 in tumors, such as hepatocellular carcinoma, highlights their prognostic significance and connection to therapeutic resistance. Cancer-associated fibroblasts and mesenchymal stromal cells produce hepatocyte growth factor (HGF), activating c-MET signaling in tumor cells and myeloid-derived suppressor cells (MDSC). This activation leads to metabolic reprogramming and increased activity of enzymes like glutaminase (GLS), indoleamine 2,3-dioxygenase (IDO), and arginase 1 (ARG1), depleting essential amino acids in the tumor microenvironment that are vital for effector immune cell function. This review highlights the interplay between tumor cells and myeloid-derived suppressor cells (MDSCs) that create an immunosuppressive environment while providing targets for c-MET-focused immunotherapy. It emphasizes the clinical implications of c-MET inhibition on the behavior of immune cells such as neutrophils, macrophages, T cells, and NK cells. It explores the potential of c-MET antagonism combined with immunotherapeutic strategies to enhance cancer treatment paradigms. This review also discusses the innovative cancer immunotherapies targeting c-MET, including chimeric antigen receptor (CAR) therapies, monoclonal antibodies, and antibody-drug conjugates, while encouraging the development of a comprehensive strategy that simultaneously tackles immune evasion and enhances anti-tumor efficacy further to improve the clinical prognoses for patients with c-MET-positive malignancies. Despite the challenges and variability in efficacy across different cancer subtypes, continued research into the molecular mechanisms and the development of innovative therapeutic strategies will be crucial. | [
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10.1007/s40265-021-01561-7 | [
"Jabbarzadeh Kaboli",
"Roozitalab",
"Farghadani",
"Eskandarian",
"Zerrouqi"
] | [
"Department of Biochemistry, Faculty of Medicine, Medical University of Warsaw, Warsaw, Poland.",
"Noncommunicable Diseases Research Center, Fasa University of Medical Sciences, Fasa, Iran.",
"Jeffrey Cheah School of Medicine and Health Sciences, Monash University Malaysia, Subang Jaya, Selangor Darul Ehsan, Malaysia.",
"Research Institute Children's Cancer Center, and Department of Pediatric Hematology and Oncology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.",
"Department of Biochemistry, Faculty of Medicine, Medical University of Warsaw, Warsaw, Poland."
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39664011 | 134 | Chimeric Antigen Receptor (CAR)-T Cells: A New Era for Hepatocellular Carcinoma Treatment. | Hepatocellular carcinoma (HCC) is one of the most common cancers and a worldwide health concern that requires novel treatment approaches. Tyrosine kinase inhibitors (TKIs) and immune checkpoint blockades (ICBs) are the current standard of care; however, their clinical benefits are limited in some advanced and metastatic patients. With the help of gene engineering techniques, a novel adoptive cellular therapy (ACT) called chimeric antigen receptor (CAR)-T cells was recently introduced for treating HCC. A plethora of current clinical and preclinical studies are attempting to improve the efficacy of CAR-T cells by dominating the immunosuppressive environment of HCC and finding the best tumor-specific antigens (TSAs). The future of care for HCC patients might be drastically improved due to the convergence of novel therapeutic methods and the continuous progress in ACT research. However, the clinical application of CAR-T cells in solid tumors is still facing several challenges. In this study, we provide an overview of the advancement and prospects of CAR-T cell immunotherapy in HCC, as well as an investigation of how cutting-edge engineering could improve CAR-T cell efficacy and safety profile. | [
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] | 2024-12-12 | 1 | 39664011 | [
"CAR)-T cells",
"HCC patients",
"novel therapeutic methods",
"HCC",
"novel treatment approaches",
"chimeric antigen receptor",
"gene engineering techniques",
"CAR-T cell efficacy",
"immune checkpoint blockades",
"solid tumors",
"CAR-T cell immunotherapy",
"CAR-T cells",
"ACT research",
"ACT",
"current clinical and preclinical studies",
"care",
"a novel adoptive cellular therapy",
"TKIs",
"several challenges",
"safety profile",
"inhibitors",
"ICBs",
"prospects",
"a worldwide health concern",
"the best tumor-specific antigens",
"their clinical benefits",
"Tyrosine",
"the clinical application",
"the current standard",
"TSAs"
] | [
"adoptive cell therapy",
"chimeric antigen receptors (CAR)‐T cell",
"hepatocellular carcinoma"
] | 0 | 10.1002/jbt.70091 | [
"Xu",
"Pan"
] | [
"Department of Liver, Gallbladder, Spleen and Stomach, Heilongjiang Academy of Chinese Mediceal Sciences, Harbin, Heilongjiang, China.",
"Department of Liver, Gallbladder, Spleen and Stomach, Heilongjiang Academy of Chinese Mediceal Sciences, Harbin, Heilongjiang, China."
] | [
"39664011"
] | [] | 10.896069 | 3.943391 |
39663681 | 135 | A Switch Protein Adapter for Anti-LILRB4 CAR-T Cells. | Chimeric antigen receptor-T cell (CAR-T) immunotherapy has shown remarkable results for the treatment of certain hematologic malignancies. A redirection strategy that utilizes clinically relevant CAR-T cells in combination with adapter proteins may be an effective strategy to target other hematologic and solid cancers. We established a fusion antibody-based strategy with flexibility to target multiple tumor types in combination with a novel anti-leukocyte immunoglobulin-like receptor-B 4 (LILRB4) CAR-T cell. Specifically, we engineered switch protein (SwP) adapters containing the LILRB4 extracellular domain fused to either an anti-CD19 or anti-CD20 single-chain variable fragment (scFv). These SwPs were sufficient to stimulate anti-LILRB4 CAR-T cells against SwP-tagged LILRB4 | [
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] | 2024-12-12 | 1 | 39663681 | [
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"other hematologic",
"adapter proteins",
"multiple tumor types",
"Chimeric antigen receptor-T cell",
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"an effective strategy",
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"A redirection strategy",
"scFv",
"CAR-T) immunotherapy",
"the treatment",
"These SwPs",
"We",
"that",
"we"
] | [
"cancer",
"chimeric antigen receptor‐T (CAR‐T)",
"inhibitory receptor",
"leukocyte immunoglobulin‐like receptor‐B 4 (LILRB4)",
"switch protein",
"tumor microenvironment",
"universal chimeric antigen receptor‐T (CAR‐T)"
] | 0 | 10.1002/eji.202451172 | [
"Huang",
"Chen",
"Xie",
"Lou",
"Tan",
"Zhang",
"An",
"John",
"Zhang"
] | [
"Department of Physiology, University of Texas Southwestern Medical Center, Dallas, Texas, USA.",
"Department of Physiology, University of Texas Southwestern Medical Center, Dallas, Texas, USA.",
"Department of Physiology, University of Texas Southwestern Medical Center, Dallas, Texas, USA.",
"Department of Physiology, University of Texas Southwestern Medical Center, Dallas, Texas, USA.",
"Texas Therapeutics Institute, Brown Foundation Institute of Molecular Medicine, University of Texas Health Science Center, Houston, Texas, USA.",
"Texas Therapeutics Institute, Brown Foundation Institute of Molecular Medicine, University of Texas Health Science Center, Houston, Texas, USA.",
"Texas Therapeutics Institute, Brown Foundation Institute of Molecular Medicine, University of Texas Health Science Center, Houston, Texas, USA.",
"Department of Pediatrics, University of Texas Southwestern Medical Center, Dallas, Texas, USA.",
"Department of Physiology, University of Texas Southwestern Medical Center, Dallas, Texas, USA."
] | [
"39663681"
] | [] | 8.294161 | 4.90145 |
39662251 | 136 | CAR-iNKT cell therapy: mechanisms, advantages, and challenges. | In recent years, chimeric antigen receptor (CAR) T-cell therapy has emerged as a groundbreaking approach in cancer immunotherapy. Particularly in hematologic malignancies, such as B-cell acute lymphoblastic leukemia (B-ALL), B cell lymphomas and multiple myeloma. CAR-T therapy has demonstrated remarkable clinical efficacy, leading to the approval of several CAR-T cell products and offering significant benefits to numerous leukemia patients. Despite these successes, the application of CAR-T cells in solid tumors remains limited due to significant challenges, including immunosuppressive tumor microenvironments, heterogeneous antigen expression, and treatment-associated toxicities. In parallel with CAR-T development, researchers are investigating other immune cell platforms to overcome these obstacles. Among these, invariant natural killer T (iNKT) cells have garnered increasing attention for their unique immunological properties. Unlike conventional T cells, iNKT cells are a subset of T lymphocytes characterized by the expression of a semi-invariant T-cell receptor (TCR) that recognizes lipid antigens presented by CD1d molecules. This distinctive antigen recognition mechanism enables iNKT cells to bridge innate and adaptive immunity, granting them potent antitumor activity and the ability to modulate the tumor microenvironment. Additionally, iNKT cells exhibit intrinsic resistance to exhaustion and an enhanced ability to infiltrate solid tumors compared to traditional T cells. Building on these properties, researchers are leveraging CAR technology to enhance iNKT cell tumor-targeting capabilities, aiming to overcome barriers encountered in solid tumor therapy. This review provides an in-depth discussion of the application and therapeutic potential of CAR-iNKT cells in cancer immunotherapy, with a focus on their advantages over conventional CAR-T cells and their role in addressing the challenges of solid tumor treatment. | [
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] | 2024-12-12 | 1 | 39662251 | [
"conventional T cells",
"traditional T cells",
"iNKT cells",
"B cell lymphomas",
"other immune cell platforms",
"solid tumor therapy",
"solid tumors",
"solid tumor treatment",
"several CAR-T cell products",
"conventional CAR-T cells",
"immunosuppressive tumor microenvironments",
"iNKT cell tumor-targeting capabilities",
"CAR-T cells",
"heterogeneous antigen expression",
"B-cell acute lymphoblastic leukemia",
"CAR-iNKT cells",
"CAR technology",
"lipid antigens",
"a semi-invariant T-cell receptor",
"significant challenges",
"T",
"chimeric antigen receptor (CAR) T-cell therapy",
"cancer immunotherapy",
"significant benefits",
"numerous leukemia patients",
"potent antitumor activity",
"remarkable clinical efficacy",
"CAR-T therapy",
"CAR-T development",
"increasing attention"
] | [
"CAR-T",
"CAR-iNKT",
"CD1d",
"Solid tumor",
"Tumor associated antigen"
] | 0 | 10.1016/j.retram.2024.103488 | [
"Wang",
"Zhang"
] | [
"Beijing Institute of Biological Products Co., Ltd, Beijing 101149, China.",
"Beijing Rongai Biotechnology Co., Ltd, 1st Floor, Building 29, No. 5 Kechuang East 2nd Street, Tongzhou District, Beijing 101100, China. Electronic address: [email protected]."
] | [
"39662251"
] | [] | 11.19841 | 5.691608 |
39660132 | 137 | Decoding NY-ESO-1 TCR T cells: transcriptomic insights reveal dual mechanisms of tumor targeting in a melanoma murine xenograft model. | The development of T cell receptor-engineered T cells (TCR-T) targeting intracellular antigens is a promising strategy for treating solid tumors; however, the mechanisms underlying their effectiveness remain poorly understood. In this study, we employed advanced techniques to investigate the functional state of T cells engineered with retroviral vectors to express a TCR specific for the NY-ESO-1 157-165 peptide in the HLA-A*02:01 context. Flow cytometry revealed a predominance of naïve T cells. Gene expression profiling using NanoString technology revealed upregulation of genes encoding chemokine receptors | [
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10.3389/fimmu.2016.00616 | [
"Alsalloum",
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] | [
"Laboratory of molecular immunology, Federal State Budgetary Scientific Institution Research Institute of Fundamental and Clinical Immunology, Novosibirsk, Russia.\nDepartment of Natural Sciences, Novosibirsk State University, Novosibirsk, Russia.",
"Laboratory of molecular immunology, Federal State Budgetary Scientific Institution Research Institute of Fundamental and Clinical Immunology, Novosibirsk, Russia.\nDepartment of Natural Sciences, Novosibirsk State University, Novosibirsk, Russia.",
"Laboratory of molecular immunology, Federal State Budgetary Scientific Institution Research Institute of Fundamental and Clinical Immunology, Novosibirsk, Russia.",
"Laboratory of molecular immunology, Federal State Budgetary Scientific Institution Research Institute of Fundamental and Clinical Immunology, Novosibirsk, Russia.",
"Laboratory of molecular immunology, Federal State Budgetary Scientific Institution Research Institute of Fundamental and Clinical Immunology, Novosibirsk, Russia.",
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"Laboratory of molecular immunology, Federal State Budgetary Scientific Institution Research Institute of Fundamental and Clinical Immunology, Novosibirsk, Russia.",
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"Center for Collective Use SPF-vivarium ICG SB RAS, Ministry of Science and High Education of Russian Federation, Novosibirsk, Russia.",
"Laboratory of molecular immunology, Federal State Budgetary Scientific Institution Research Institute of Fundamental and Clinical Immunology, Novosibirsk, Russia.",
"Department of Personalized Cancer Immunotherapy, Mie University Graduate School of Medicine, Tsu, Japan.",
"Laboratory of molecular immunology, Federal State Budgetary Scientific Institution Research Institute of Fundamental and Clinical Immunology, Novosibirsk, Russia.",
"Laboratory of molecular immunology, Federal State Budgetary Scientific Institution Research Institute of Fundamental and Clinical Immunology, Novosibirsk, Russia.\nDepartment of Immunology, V. Zelman Institute for Medicine and Psychology, Novosibirsk State University, Novosibirsk, Russia."
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39659785 | 138 | Recommendations for the effective use of T-cell-redirecting therapies: a Canadian consensus statement. | T-cell-redirecting therapies, such as bispecific antibodies and chimeric antigen receptor T-cells, exploit the cytotoxic capabilities of the immune system to destroy cells expressing specific surface antigens, including malignant cells. These therapies have demonstrated unprecedented rates, depth, and duration of responses in relapsed and refractory multiple myeloma. However, there are significant challenges in implementing these therapies into practice, which require multidisciplinary and multicenter coordination and significant healthcare resources to effectively manage these patients. So far, there are no Canadian guidelines for the effective implementation and use of T-cell-redirecting therapies.
This consensus statement was developed based on three advisory meetings held in March, July, and November 2023. During these meetings, a panel of Canadian subject matter experts and representation from Myeloma Canada gathered to discuss the optimal procedures for the use of T-cell-redirecting therapies in the treatment of multiple myeloma. Members of the panel performed a thorough review of randomized clinical trials, real-world data, and other current literature, and provided their up-to-date clinical experience with T-cell-redirecting therapies in Canadian practice settings. Subsequently, asynchronous working groups were appointed to develop unified criteria for patient selection, appraise referral pathways, and devise strategies for management of short-term and long-term adverse events arising from the use of T-cell-redirecting therapies in multiple myeloma.
Here, we present recommendations for optimizing patient selection, referral pathways, and adverse event management in the Canadian practice setting. These recommendations are relevant for hematologists/oncologists, oncology nurses, pharmacists, nurse practitioners, physician assistants, and other providers who treat patients with multiple myeloma, as well as individuals with multiple myeloma and their care partners. These recommendations will be of interest to clinicians who treat patients with MM at community clinics and hospitals and who may be interested in referring patients for T-cell-redirecting therapy. | [
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39659573 | 139 | Revolutionizing cancer treatment: the emerging potential and potential challenges of | Chimeric antigen receptor (CAR) cell immunotherapies, including CAR-T, CAR-Macrophages, CAR-Natural Killer, CAR-γδ T, etc., have demonstrated significant advancements in the treatment of both hematologic malignancies and solid tumors. Despite the notable successes of traditional CAR cell manufacturing, its application remains constrained by the complicated production process and expensive costs. Consequently, efforts are focused on streamlining CAR cell production to enhance efficacy and accessibility. Among numerous proposed strategies, direct | [
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] | 2024-12-11 | 196 | 39659573 | [
"CAR cell production",
"traditional CAR cell manufacturing",
"cell immunotherapies",
"CAR",
"numerous proposed strategies",
"significant advancements",
"Chimeric antigen receptor",
"CAR-γδ T",
"solid tumors",
"expensive costs",
"CAR-Natural Killer",
"the complicated production process",
"CAR-T",
"CAR-Macrophages",
"efficacy",
"accessibility",
"efforts",
"both hematologic malignancies",
"the notable successes",
"the treatment",
"its application"
] | [
"CAR",
"Construction",
"Delivery technology",
"Immunotherapy",
"Vector particles"
] | 0 | 10.7150/thno.101941 | [
"Lv",
"Guo",
"Liu",
"Dong",
"Liu",
"Li",
"Ren",
"Zhang",
"Neo",
"Mao",
"Wu"
] | [
"Department of Pharmacy, The First Affiliated Hospital of Shandong First Medical University & Shandong Provincial Qianfoshan Hospital; Jinan 250014, China; School of Pharmacy, Shandong First Medical University & Shandong Academy of Medical Sciences, Jinan, Shandong 250117, China.",
"Department of Pharmacy, The First Affiliated Hospital of Shandong First Medical University & Shandong Provincial Qianfoshan Hospital; Jinan 250014, China; School of Pharmacy, Shandong First Medical University & Shandong Academy of Medical Sciences, Jinan, Shandong 250117, China.",
"Department of Thoracic Surgery, The Affiliated Wuxi People's Hospital of Nanjing Medical University, Wuxi People's Hospital, Wuxi Medical Center, Nanjing Medical University, Wuxi, Jiangsu 214023, China.",
"Department of Pharmacy, The First Affiliated Hospital of Shandong First Medical University & Shandong Provincial Qianfoshan Hospital; Jinan 250014, China; School of Pharmacy, Shandong First Medical University & Shandong Academy of Medical Sciences, Jinan, Shandong 250117, China.",
"Department of Pharmacy, The First Affiliated Hospital of Shandong First Medical University & Shandong Provincial Qianfoshan Hospital; Jinan 250014, China; School of Pharmacy, Shandong First Medical University & Shandong Academy of Medical Sciences, Jinan, Shandong 250117, China.",
"Department of Pharmacy, The First Affiliated Hospital of Shandong First Medical University & Shandong Provincial Qianfoshan Hospital; Jinan 250014, China; School of Pharmacy, Shandong First Medical University & Shandong Academy of Medical Sciences, Jinan, Shandong 250117, China.",
"Department of Clinical Pharmacy, School of Pharmacy, Shandong Second Medical University, Weifang, Shandong 261042, China.",
"Medical Science and Technology Innovation Center Shandong First Medical University & Shandong Academy of Medical Sciences Jinan 250117, China.",
"Singapore Immunology Network, Agency for Science, Technology and Research, Singapore 138648, Republic of Singapore.",
"Department of Thoracic Surgery, The Affiliated Wuxi People's Hospital of Nanjing Medical University, Wuxi People's Hospital, Wuxi Medical Center, Nanjing Medical University, Wuxi, Jiangsu 214023, China.",
"Department of Pharmacy, The First Affiliated Hospital of Shandong First Medical University & Shandong Provincial Qianfoshan Hospital; Jinan 250014, China; School of Pharmacy, Shandong First Medical University & Shandong Academy of Medical Sciences, Jinan, Shandong 250117, China."
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] | [] | 8.630217 | 3.563142 |
39658572 | 140 | Cullin-5 deficiency promotes chimeric antigen receptor T cell effector functions potentially via the modulation of JAK/STAT signaling pathway. | Chimeric antigen receptor (CAR) T cell is a promising therapy for cancer, but factors that enhance the efficacy of CAR T cell remain elusive. Here we perform a genome-wide CRISPR screening to probe genes that regulate the proliferation and survival of CAR T cells following repetitive antigen stimulations. We find that genetic ablation of CUL5, encoding a core element of the multi-protein E3 ubiquitin-protein ligase complex, cullin-RING ligase 5, enhances human CD19 CAR T cell expansion potential and effector functions, potentially via the Janus kinase/signal transducers and activators of transcription (JAK/STAT) pathway. In this regard, CUL5 knockout CD19 CAR T cells show sustained STAT3 and STAT5 phosphorylation, as well as delayed phosphorylation and degradation of JAK1 and JAK3. In vivo, shRNA-mediated knockdown of CUL5 enhances CD19 CAR T treatment outcomes in tumor-bearing mice. Our findings thus imply that targeting CUL5 in the ubiquitin system may enhance CAR T cell effector functions to enhance immunotherapy efficacy. | [
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] | 2024-12-11 | 65 | 39658572 | [
"CAR T cell",
"CAR T cells",
"CUL5 knockout CD19 CAR T cells",
"CAR T cell effector functions",
"CUL5 enhances CD19 CAR T treatment outcomes",
"human CD19 CAR T cell expansion potential and effector functions",
"CAR",
"CUL5",
"delayed phosphorylation",
"repetitive antigen stimulations",
"immunotherapy efficacy",
"the multi-protein E3 ubiquitin-protein ligase complex",
"CRISPR",
"transcription",
"activators",
"genes",
"STAT5",
"E3",
"degradation",
"STAT3",
"STAT3 and STAT5 phosphorylation",
"Janus",
"survival",
"cancer",
"factors",
"JAK1",
"pathway",
"the ubiquitin system",
"JAK3",
"vivo"
] | [] | 0 | 10.1038/s41467-024-54794-x | [
"Adachi",
"Terakura",
"Osaki",
"Okuno",
"Sato",
"Sagou",
"Takeuchi",
"Yokota",
"Imai",
"Steinberger",
"Leitner",
"Hanajiri",
"Murata",
"Kiyoi"
] | [
"Department of Hematology and Oncology, Nagoya University Graduate School of Medicine, Nagoya, Japan. [email protected].",
"Department of Hematology and Oncology, Nagoya University Graduate School of Medicine, Nagoya, Japan. [email protected].",
"Department of Hematology and Oncology, Nagoya University Graduate School of Medicine, Nagoya, Japan.",
"Department of Virology, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan.",
"Department of Virology, Nagoya University Graduate School of Medicine, Nagoya, Japan.",
"Department of Hematology and Oncology, Nagoya University Graduate School of Medicine, Nagoya, Japan.\nDepartment of Virology, Nagoya University Graduate School of Medicine, Nagoya, Japan.",
"Department of Hematology and Oncology, Nagoya University Graduate School of Medicine, Nagoya, Japan.",
"Department of Hematology and Oncology, Nagoya University Graduate School of Medicine, Nagoya, Japan.",
"Department of Hematology and Oncology, Nagoya University Graduate School of Medicine, Nagoya, Japan.",
"Division for Immune Receptors and T Cell Activation, Institute of Immunology, Medical University of Vienna, Vienna, Austria.",
"Division for Immune Receptors and T Cell Activation, Institute of Immunology, Medical University of Vienna, Vienna, Austria.",
"Department of Hematology and Oncology, Nagoya University Graduate School of Medicine, Nagoya, Japan.",
"Department of Hematology and Oncology, Nagoya University Graduate School of Medicine, Nagoya, Japan.",
"Department of Hematology and Oncology, Nagoya University Graduate School of Medicine, Nagoya, Japan."
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39657679 | 141 | Patient-derived glioblastoma organoids as real-time avatars for assessing responses to clinical CAR-T cell therapy. | Patient-derived tumor organoids have been leveraged for disease modeling and preclinical studies but rarely applied in real time to aid with interpretation of patient treatment responses in clinics. We recently demonstrated early efficacy signals in a first-in-human, phase 1 study of dual-targeting chimeric antigen receptor (CAR)-T cells (EGFR-IL13Rα2 CAR-T cells) in patients with recurrent glioblastoma. Here, we analyzed six sets of patient-derived glioblastoma organoids (GBOs) treated concurrently with the same autologous CAR-T cell products as patients in our phase 1 study. We found that CAR-T cell treatment led to target antigen reduction and cytolysis of tumor cells in GBOs, the degree of which correlated with CAR-T cell engraftment detected in patients' cerebrospinal fluid (CSF). Furthermore, cytokine release patterns in GBOs mirrored those in patient CSF samples over time. Our findings highlight a unique trial design and GBOs as a valuable platform for real-time assessment of CAR-T cell bioactivity and insights into immunotherapy efficacy. | [
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] | 2024-12-11 | 1 | 39657679 | [
"tumor cells",
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] | [
"CAR-T cell therapy",
"clinical trial",
"cytokine",
"ex vivo",
"glioblastoma",
"organoid",
"patient-derived tumor organoid",
"real-time correlative"
] | 0 | 10.1016/j.stem.2024.11.010 | [
"Logun",
"Wang",
"Sun",
"Bagley",
"Li",
"Desai",
"Zhang",
"Nasrallah",
"Pai",
"Oner",
"Plesa",
"Siegel",
"Binder",
"Ming",
"Song",
"O'Rourke"
] | [
"Glioblastoma Translational Center of Excellence, Abramson Cancer Center, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA; Department of Neurosurgery, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA.",
"Department of Neuroscience and Mahoney Institute for Neurosciences, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA.",
"Neuroscience Graduate Group, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA.",
"Department of Neurosurgery, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA; Division of Hematology/Oncology, Department of Medicine, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA.",
"Glioblastoma Translational Center of Excellence, Abramson Cancer Center, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA; Department of Neurosurgery, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA.",
"Department of Neurosurgery, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA; Division of Hematology/Oncology, Department of Medicine, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA.",
"Department of Neurosurgery, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA.",
"Glioblastoma Translational Center of Excellence, Abramson Cancer Center, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA; Department of Pathology and Laboratory Medicine, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA.",
"Center for Cellular Immunotherapies, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA.",
"Center for Cellular Immunotherapies, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA.",
"Center for Cellular Immunotherapies, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA.",
"Glioblastoma Translational Center of Excellence, Abramson Cancer Center, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA; Department of Pathology and Laboratory Medicine, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA; Center for Cellular Immunotherapies, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA.",
"Glioblastoma Translational Center of Excellence, Abramson Cancer Center, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA; Department of Neurosurgery, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA; Center for Cellular Immunotherapies, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA. Electronic address: [email protected].",
"Department of Neuroscience and Mahoney Institute for Neurosciences, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA; Institute for Regenerative Medicine, University of Pennsylvania, Philadelphia, PA, USA; Department of Cell and Developmental Biology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA; Department of Psychiatry, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA. Electronic address: [email protected].",
"Glioblastoma Translational Center of Excellence, Abramson Cancer Center, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA; Department of Neurosurgery, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA; Department of Neuroscience and Mahoney Institute for Neurosciences, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA; Institute for Regenerative Medicine, University of Pennsylvania, Philadelphia, PA, USA; Department of Cell and Developmental Biology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA; Epigenetics Institute, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA. Electronic address: [email protected].",
"Glioblastoma Translational Center of Excellence, Abramson Cancer Center, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA; Department of Neurosurgery, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA; Center for Cellular Immunotherapies, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA. Electronic address: [email protected]."
] | [
"39657679"
] | [] | 9.977834 | 7.248429 |
39655500 | 142 | Novel strategies to assess cytokine release mediated by chimeric antigen receptor T cells based on the adverse outcome pathway concept. | The success of cellular immunotherapies such as chimeric antigen receptor (CAR) T cell therapy has led to their implementation as a revolutionary treatment option for cancer patients. However, the safe translation of such novel immunotherapies, from non-clinical assessment to first-in-human studies is still hampered by the lack of suitable | [
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] | 2024-12-10 | 1 | 39655500 | [
"such novel immunotherapies",
"non-clinical assessment",
"T cell therapy",
"chimeric antigen receptor",
"cellular immunotherapies",
"cancer patients",
"first",
"CAR",
"a revolutionary treatment option",
"the safe translation",
"first-in-human studies",
"their implementation",
"the lack",
"The success"
] | [
"CAR T cells",
"biomarkers",
"cytokine release syndrome",
"immune-related adverse outcome pathway",
"non-clinical safety assessment",
"organ-on-a-chip"
] | 0 | 10.1080/1547691X.2024.2345158 | [
"Alb",
"Reiche",
"Rade",
"Sewald",
"Loskill",
"Cipriano",
"Maulana",
"van der Meer",
"Weener",
"Clerbaux",
"Fogal",
"Patel",
"Adkins",
"Lund",
"Perkins",
"Cooper",
"van den Brulle",
"Morgan",
"Rubic-Schneider",
"Ling",
"DiPetrillo",
"Moggs",
"Köhl",
"Hudecek"
] | [
"Medizinische Klinik und Poliklinik II, Lehrstuhl für Zelluläre Immuntherapie, Universitätsklinikum Würzburg, Würzburg, Germany.",
"Fraunhofer-Institut für Zelltherapie und Immunologie IZI, Leipzig, Germany.",
"Fraunhofer-Institut für Zelltherapie und Immunologie IZI, Leipzig, Germany.",
"Fraunhofer-Institut für Toxikologie und Experimentelle Medizin ITEM, Hannover, Germany.",
"Institute for Biomedical Engineering, Eberhard Karls University Tübingen, Tübingen, Germany.\n3R-Center for In vitro Models and Alternatives to Animal Testing, Eberhard Karls University Tübingen, Tübingen.\nNMI Natural and Medical Sciences Institute at the University of Tübingen, Reutlingen, Germany.",
"Institute for Biomedical Engineering, Eberhard Karls University Tübingen, Tübingen, Germany.\n3R-Center for In vitro Models and Alternatives to Animal Testing, Eberhard Karls University Tübingen, Tübingen.",
"Institute for Biomedical Engineering, Eberhard Karls University Tübingen, Tübingen, Germany.\n3R-Center for In vitro Models and Alternatives to Animal Testing, Eberhard Karls University Tübingen, Tübingen.",
"Applied Stem Cell Technologies, University of Twente, Enschede, the Netherlands.",
"Applied Stem Cell Technologies, University of Twente, Enschede, the Netherlands.",
"European Commission, Joint Research Centre (JRC), Ispra, Italy.",
"Department on Nonclinical Drug Safety, Boehringer Ingelheim Pharmaceutical, Inc, Ridgefield, CT, USA.",
"Preclinical Safety, Research and Development, Sanofi-Aventis US, LLC, Cambridge, MA, USA.",
"Preclinical Safety, Research and Development, Sanofi-Aventis US, LLC, Cambridge, MA, USA.",
"Labcorp Drug Development Inc, Derbyshire, UK.",
"Labcorp Drug Development Inc, Derbyshire, UK.",
"Labcorp Drug Development Inc, Derbyshire, UK.",
"T-CURX GmbH, Würzburg, Germany.",
"Novartis Biomedical Research, Novartis Campus, Basel, Switzerland.",
"Novartis Biomedical Research, Novartis Campus, Basel, Switzerland.",
"Novartis Biomedical Research, Cambridge, MA, USA.",
"Novartis Biomedical Research, Cambridge, MA, USA.",
"Novartis Biomedical Research, Novartis Campus, Basel, Switzerland.",
"Fraunhofer-Institut für Zelltherapie und Immunologie IZI, Leipzig, Germany.",
"Medizinische Klinik und Poliklinik II, Lehrstuhl für Zelluläre Immuntherapie, Universitätsklinikum Würzburg, Würzburg, Germany.\nFraunhofer-Institut für Zelltherapie und Immunologie IZI, Leipzig, Germany."
] | [
"39655500"
] | [] | 8.722438 | 3.859019 |
39655466 | 143 | Mapping the Clinical Development Trajectory of Cell and Gene Therapy Products. | While cell and gene therapies (CGTs) have emerged as promising modalities to treat conditions with limited therapeutic options, their unconventional development is fraught with uncertainty, rendering them high-risk assets for many pharmaceutical companies. Here, we assess the clinical development trajectories of CGT products by estimating probabilities of successful clinical trial phase transitions and the likelihood of achieving regulatory approval. We included all CGT products entering clinical development from 1993 to 2023 and intended for marketing in the United States, Europe, Japan, Canada, and Switzerland. Associations between product success and characteristics were investigated. In sub-analyses, we examined the clinical trajectories of two promising product types, chimeric antigen receptor T (CAR T) cell therapies and adeno-associated viral (AAV) vector-based gene therapies. We identified 995 CGT products corresponding to 1,961 development programs. A total of 44 CGTs secured at least one regulatory approval, corresponding to an overall likelihood of approval of 5.3% (95% CI 4.0-6.9). Development programs with an orphan designation had a higher likelihood of approval than those without (9.4%, 95% CI 6.6-13.3 vs. 3.2%, 95% CI 2.0-4.9), while programs for oncology indications had a lower likelihood of approval compared to those for non-oncology indications (3.2%, 95% CI 1.6-5.1 vs. 8.0%, 95% CI 5.7-11.1). CAR T cells and AAV gene therapies had a similar overall likelihood of approval of 13.6% (95% CI 7.3, 23.9) and 13.6% (95% CI 6.4, 26.7), respectively. In conclusion, CGT products have a low overall likelihood of approval with variability based on orphan status, therapeutic area, and product type. | [
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] | [] | 0 | 10.1002/cpt.3512 | [
"Elsallab",
"Ouvina",
"Arfe",
"Bourgeois"
] | [
"Harvard-MIT Center for Regulatory Science, Harvard Medical School, Boston, Massachusetts, USA.\nCellular Immunotherapy Program, Mass General Cancer Center and Department of Medicine, Harvard Medical School, Boston, Massachusetts, USA.",
"Computational Health Informatics Program, Boston Children's Hospital, Boston, Massachusetts, USA.",
"Memorial Sloan Kettering Cancer Center, New York, New York, USA.",
"Harvard-MIT Center for Regulatory Science, Harvard Medical School, Boston, Massachusetts, USA.\nComputational Health Informatics Program, Boston Children's Hospital, Boston, Massachusetts, USA.\nDepartment of Pediatrics, Harvard Medical School, Boston, Massachusetts, USA."
] | [
"39655466"
] | [] | 9.035929 | 3.256599 |
39654883 | 144 | From metabolic byproduct to immune modulator: the role of lactate in tumor immune escape. | Lactic acid, a key metabolic byproduct within the tumor microenvironment, has garnered significant attention for its role in immune evasion mechanisms. Tumor cells produce and release large amounts of lactic acid into the tumor microenvironment through aberrant glycolysis via the Warburg effect, leading to a drop in pH. Elevated lactic acid levels profoundly suppress proliferation capacity, cytotoxic functions, and migratory abilities of immune effector cells such as macrophages and natural killer cells at the tumor site. Moreover, lactic acid can modulate the expression of surface molecules on immune cells, interfering with their recognition and attack of tumor cells, and it regulates signaling pathways that promote the expansion and enhanced function of immunosuppressive cells like regulatory T cells, thereby fostering immune tolerance within the tumor microenvironment. Current research is actively exploring strategies targeting lactic acid metabolism to ameliorate tumor immune evasion. Key approaches under investigation include inhibiting the activity of critical enzymes in lactic acid production to reduce its synthesis or blocking lactate transporters to alter intracellular and extracellular lactate distribution. These methods hold promise when combined with existing immunotherapies such as immune checkpoint inhibitors and chimeric antigen receptor T-cell therapies to enhance the immune system's ability to eliminate tumor cells. This could pave the way for novel combinatorial treatment strategies in clinical cancer therapy, effectively overcoming tumor immune evasion phenomena, and ultimately improving overall treatment efficacy. | [
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"tumor immune evasion",
"immune cells",
"Tumor cells",
"tumor cells",
"tumor immune evasion phenomena",
"immune effector cells",
"Lactic acid",
"lactic acid",
"lactic acid production",
"lactic acid metabolism",
"pH. Elevated lactic acid levels",
"immune evasion mechanisms",
"immune checkpoint inhibitors",
"immune tolerance",
"immunosuppressive cells",
"natural killer cells",
"regulatory T cells",
"novel combinatorial treatment strategies",
"clinical cancer therapy",
"chimeric antigen receptor T-cell therapies",
"enhanced function",
"overall treatment efficacy",
"cytotoxic functions",
"lactate transporters",
"migratory abilities",
"strategies",
"existing immunotherapies",
"the tumor microenvironment",
"Key approaches",
"critical enzymes"
] | [
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"immune evasion",
"lactic acid",
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10.3389/fonc.2020.598626 | [
"Jiang",
"Wang",
"Zhao",
"Yu"
] | [
"School of Clinical Medicine, Shandong Second Medical University, Weifang, China.\nDepartment of Radiation Oncology and Shandong Provincial Key Laboratory of Precision Oncology, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, Shandong, China.",
"Laboratory of Anesthesia and Critical Care Medicine in Colleges and Universities of Shandong Province, School of Anesthesiology, Shandong Second Medical University, Weifang, China.",
"Department of Anesthesiology, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, Shandong, China.",
"School of Clinical Medicine, Shandong Second Medical University, Weifang, China.\nDepartment of Radiation Oncology and Shandong Provincial Key Laboratory of Precision Oncology, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, Shandong, China.\nResearch Unit of Radiation Oncology, Chinese Academy of Medical Sciences, Jinan, Shandong, China."
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39653553 | 145 | CAR T cells secreting NGF-neutralizing scFv enhance efficacy in clear cell renal cell carcinoma by relieving immunosuppression through immunosympathectomy. | Chimeric antigen receptor (CAR) T cells have demonstrated remarkable breakthroughs in treating hematologic malignancies, yet their efficacy in solid tumors is limited by the immunosuppressive microenvironment. Sympathetic nerves significantly contribute to this immunosuppressive milieu in solid tumors. However, the impact of tumor sympathetic denervation on enhancing CAR T-cell antitumor efficacy remains unclear.
We screened for sympathetic gene sets in various types of cancers and investigated the association of sympathetic nerves with immunosuppression in renal clear cell carcinoma. Using antibodies to block the nerve growth factor (NGF) pathway, we explored sympathetic nerve distribution in tumor tissues and tumor progression. Additionally, we engineered CAR T cells to secrete NGF single chain fragment variable (scFv) to achieve tumor immunosympathectomy and assessed their antitumor efficacy. Bulk RNA sequencing and single-cell RNA sequencing analyses were conducted to evaluate changes in immune cell phenotypes within the tumor microenvironment.
Blocking the NGF pathway with antibodies effectively reduced sympathetic nerve distribution in tumor tissues and delayed tumor progression. CAR T cells engineered to secrete NGF scFv achieved a similar tumor immunosympathectomy and exhibited enhanced tumor suppression. RNA sequencing analyses revealed that this augmented effect was primarily due to the inhibition of the terminal exhaustion phenotype in tumor-infiltrating CD8 T cells and the prevention of macrophage polarization from M1 to M2. This approach maintained a stronger antitumor immune state at the tumor site. Additionally, splenic T cells also exhibited a more potent immune effector phenotype following the infusion of NGF scFv-secreting CAR T cells.
Our results suggest that immunosympathectomy is a novel approach to weaken tumor microenvironment immunosuppression and synergistically enhance CAR T-cell efficacy against solid tumors. | [
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"the tumor site",
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] | [
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10.1172/JCI43490 | [
"Yang",
"Chen",
"Yu",
"Wang",
"Li",
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] | [
"The Engineering Research Center of Synthetic Polypeptide Drug Discovery and Evaluation, Jiangsu Province, China Pharmaceutical University, Nanjing, Jiangsu Province, China.\nState Key Laboratory of Natural Medicines, Ministry of Education, China Pharmaceutical University, Nanjing, China.",
"The Engineering Research Center of Synthetic Polypeptide Drug Discovery and Evaluation, Jiangsu Province, China Pharmaceutical University, Nanjing, Jiangsu Province, China.\nState Key Laboratory of Natural Medicines, Ministry of Education, China Pharmaceutical University, Nanjing, China.",
"The Engineering Research Center of Synthetic Polypeptide Drug Discovery and Evaluation, Jiangsu Province, China Pharmaceutical University, Nanjing, Jiangsu Province, China.\nState Key Laboratory of Natural Medicines, Ministry of Education, China Pharmaceutical University, Nanjing, China.",
"NHC Key Laboratory of Research on Quality and Standardization of Biotech Products, NMPA Key Laboratory for Quality Research and Evaluation of Biological Products, State Key Laboratory of Drug Regulatory Science, National Institutes for Food and Drug Control, Beijing, China.",
"NHC Key Laboratory of Research on Quality and Standardization of Biotech Products, NMPA Key Laboratory for Quality Research and Evaluation of Biological Products, State Key Laboratory of Drug Regulatory Science, National Institutes for Food and Drug Control, Beijing, China.",
"The Engineering Research Center of Synthetic Polypeptide Drug Discovery and Evaluation, Jiangsu Province, China Pharmaceutical University, Nanjing, Jiangsu Province, China.\nState Key Laboratory of Natural Medicines, Ministry of Education, China Pharmaceutical University, Nanjing, China.",
"The Engineering Research Center of Synthetic Polypeptide Drug Discovery and Evaluation, Jiangsu Province, China Pharmaceutical University, Nanjing, Jiangsu Province, China [email protected].\nState Key Laboratory of Natural Medicines, Ministry of Education, China Pharmaceutical University, Nanjing, China."
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39652252 | 146 | Advancing Systemic Therapy in Chondrosarcoma: New Horizons. | The systemic treatment landscape for advanced and metastatic chondrosarcoma, a malignancy with limited responsiveness to conventional therapies, has always been notoriously challenging. While standard chemotherapy offers minimal benefits, certain subtypes, such as mesenchymal and dedifferentiated chondrosarcomas, have shown some response to systemic therapies initially developed for other sarcomas. Investigational strategies are focusing on molecular targets, including mutations in the isocitrate dehydrogenase gene (IDH), signaling pathways, such as hedgehog and death receptor 5 (DR5) and immune modulation. IDH mutations, notably found in conventional and dedifferentiated chondrosarcomas, have prompted the evaluation of IDH inhibitors, which have demonstrated promising efficacy in preclinical and early clinical trials, despite limited data in chondrosarcoma. Additionally, the hedgehog pathway, implicated in chondrosarcoma progression, has been targeted with inhibitors, although clinical translation has shown mixed results. Immunotherapy, including programmed cell death 1 (PD-1) checkpoint inhibitors and chimeric antigen receptor-T (CAR-T) cells, is also being investigated but faces challenges due to the immunosuppressive tumour microenvironment. Among new approaches, DR5 agonists such as INBRX-109 have shown single-agent efficacy, with minimal toxicity, opening possibilities for use in combination therapies to improve outcomes. Given the heterogenous and treatment-resistant nature of chondrosarcoma, we highlight the need for multi-omics and genetic profiling to guide personalized, combination therapies that target multiple carcinogenic pathways. The integration of multi-targeted approaches could enhance efficacy, address tumour heterogeneity, and overcome resistance, presenting a hopeful direction for systemic therapy in this challenging cancer. The investigation of combination regimens with IDH inhibitors, immunotherapy and DR5 agonists hold promise for transforming the management of advanced chondrosarcoma. | [
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39652017 | 147 | Efficient manufacturing of CAR-T cells from whole blood: a scalable approach to reduce costs and enhance accessibility in cancer therapy. | Chimeric antigen receptor T (CAR-T) cells have significantly advanced the treatment of cancers such as leukemia and lymphoma. Traditionally, T cells are collected from patients through leukapheresis, an expensive and potentially invasive process that requires specialized equipment and trained personnel. Although whole blood collections are much more technically straightforward, whole blood starting material has not been widely utilized for clinical CAR-T cell manufacturing, in part due to lack of manufacturing processes designed for use in a good manufacturing practice (GMP) environment. Collecting cellular starting material from whole blood without leukapheresis could reduce manufacturing complexity and cost, thereby improving accessibility to CAR-T cell therapy.
Whole blood samples were collected from eight healthy donors and one pediatric B-cell acute lymphoblastic leukemia (B-ALL) patient. These samples were processed using the Sepax C-Pro (Cytiva) instrument to isolate mononuclear cells (MNCs) via density gradient separation. CAR-T cells were then manufactured from the isolated MNCs using a GMP-compliant 7-day protocol, whereby T cells were activated with anti-CD3 and IL-2, transduced with GMP lentiviral vector encoding a CD19/CD22 bispecific CAR, and expanded in gas permeable cell culture bags. The resulting CAR-T cells were then evaluated for their phenotypic and functional properties using flow cytometry, cytokine release and cytotoxicity assays.
From an average 77.7 mL of whole blood from healthy donors (range = 29-96 mL), we isolated an average of 42.2 × 10
Therapeutically relevant doses of CD19/CD22 CAR-T cells can be successfully manufactured from whole blood. On average, 80 mL of whole blood yields enough CAR-T cells to create a single dose for a pediatric patient (50 kg) at a dosage of 1 × 10 | [
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] | [
"cell manufacturing",
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] | 0 | 10.1016/j.jcyt.2024.11.013 | [
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] | [
"Department of Transfusion Medicine, Center for Cellular Engineering, National Institutes of Health, Bethesda, Maryland, USA.",
"Department of Transfusion Medicine, Center for Cellular Engineering, National Institutes of Health, Bethesda, Maryland, USA.",
"Department of Transfusion Medicine, Center for Cellular Engineering, National Institutes of Health, Bethesda, Maryland, USA.",
"Department of Transfusion Medicine, Center for Cellular Engineering, National Institutes of Health, Bethesda, Maryland, USA.",
"Department of Transfusion Medicine, Center for Cellular Engineering, National Institutes of Health, Bethesda, Maryland, USA.",
"Department of Transfusion Medicine, Center for Cellular Engineering, National Institutes of Health, Bethesda, Maryland, USA.",
"Department of Transfusion Medicine, Center for Cellular Engineering, National Institutes of Health, Bethesda, Maryland, USA.",
"Department of Transfusion Medicine, Center for Cellular Engineering, National Institutes of Health, Bethesda, Maryland, USA.",
"Pediatric Oncology Branch, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA.",
"Pediatric Oncology Branch, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA.",
"Department of Transfusion Medicine, Center for Cellular Engineering, National Institutes of Health, Bethesda, Maryland, USA.",
"Department of Transfusion Medicine, Center for Cellular Engineering, National Institutes of Health, Bethesda, Maryland, USA.",
"Pediatric Oncology Branch, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA.",
"Department of Transfusion Medicine, Center for Cellular Engineering, National Institutes of Health, Bethesda, Maryland, USA.",
"Department of Transfusion Medicine, Center for Cellular Engineering, National Institutes of Health, Bethesda, Maryland, USA.",
"Department of Transfusion Medicine, Center for Cellular Engineering, National Institutes of Health, Bethesda, Maryland, USA.",
"Department of Transfusion Medicine, Center for Cellular Engineering, National Institutes of Health, Bethesda, Maryland, USA. Electronic address: [email protected]."
] | [
"39652017"
] | [] | 8.554451 | 3.061768 |
39651553 | 148 | Idecabtagene vicleucel (ide-cel) for the treatment of triple-class exposed relapsed and refractory multiple myeloma. | Modern anti-myeloma therapies have broken new ground in the treatment of the disease, and the incorporation of ide-cel in the treatment landscape represents one of the major scientific and clinical advances.
Ide-cel was the first cell-based gene therapy approved for the treatment of triple-class exposed relapsed/refractory myeloma patients, showing impressive results, and demonstrating superiority over standard regimens in terms of efficacy, potential treatment-free intervals, and improved quality of life in heavily pretreated patients and in high-risk disease. This review summarizes the state-of-the-art of the most recent updates deriving from the use of ide-cel within ongoing, or upcoming, clinical trials, and from real-life experiences.
As the use of chimeric antigen receptor (CAR)-T therapy is likely to progressively increase over time and current indications expand to earlier treatment lines, efforts should be directed toward ameliorating overall management to facilitate proactive planning for treatment sequencing and provide adequate time for logistical planning. Importantly, the potential limited availability of CAR-T therapy highlights the importance of careful patient selection and coordination among centers. Meanwhile, attempts are underway to improve tolerance and reduce toxicity while enhancing anti-myeloma activity. | [
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"IRCCS Azienda Ospedaliero-Universitaria di Bologna, Istituto di Ematologia \"Seràgnoli\", Bologna, Italy.",
"IRCCS Azienda Ospedaliero-Universitaria di Bologna, Istituto di Ematologia \"Seràgnoli\", Bologna, Italy.",
"IRCCS Azienda Ospedaliero-Universitaria di Bologna, Istituto di Ematologia \"Seràgnoli\", Bologna, Italy.",
"IRCCS Azienda Ospedaliero-Universitaria di Bologna, Istituto di Ematologia \"Seràgnoli\", Bologna, Italy.",
"IRCCS Azienda Ospedaliero-Universitaria di Bologna, Istituto di Ematologia \"Seràgnoli\", Bologna, Italy.",
"Dipartimento di Scienze Mediche e Chirurgiche, Università di Bologna, Bologna, Italy."
] | [
"39651553"
] | [] | 5.072987 | 6.243235 |
39651170 | 149 | Paired CRISPR screens to map gene regulation in | Recent massively-parallel approaches to decipher gene regulatory circuits have focused on the discovery of either | [
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] | 2024-12-09 | 1 | 39651170 | [
"decipher gene regulatory circuits",
"Recent massively-parallel approaches",
"the discovery",
"either"
] | [] | 0 | 10.1101/2024.11.27.625752 | [
"Xue",
"Gajic",
"Caragine",
"Legut",
"Walker",
"Kim",
"Wang",
"Yan",
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"39651170"
] | [] | 33.390869 | 7.359536 |
39651060 | 150 | A Discount on the Cost of Cancer: India's Homegrown CAR-T Cell Therapy. | Chimeric antigen receptor T cell (CAR-T) therapy has revolutionized the treatment of blood cancer. By improving survival outcomes for patients with B-cell malignancies, which hitherto have been unparalleled by conventional chemotherapy, CAR-T therapy is a beacon of hope for many patients with cancer. However, harvesting, modifying, and reintroducing T cells is costly, which means that not every patient with cancer who needs CAR-T therapy has the financial capacity to receive it. This blatant economic disparity, combined with geographical limitations, for several lower-middle-income countries that do not manufacture CAR-T therapy, has been a problem that has widened the socioeconomic gap between patients with cancer. This was the case until India recently manufactured its own CAR-T therapy. As a lower-middle-income country with a massive burden of cancer, India's NexCAR19 was a pivotal point in South Asian cancer history. From benefiting local patients with cancer to collaborations with neighboring countries, to prompting the manufacture of more CAR-T products, NexCAR19 has facilitated the fight against blood cancers in South Asia. | [
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] | 0 | 10.31547/bct-2024-008 | [
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] | [
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39644098 | 151 | A Pathologist's Guide to Non-clinical Safety Assessment of Adoptive Cell Therapy Products. | Through two decades of research and development, adoptive cell therapies (ACTs) have revolutionized treatment for hematologic malignancies. Many of the seven US Food and Drug Administration (FDA)-approved products are proven to be a curative last line of defense against said malignancies. The ACTs, known more commonly as chimeric antigen receptor (CAR) T-cells, utilize engineered lymphocytes to target and destroy cancer cells in a patient-specific, major histocompatibility complex (MHC)-independent manner, acting as "living drugs" that adapt to and surveil the body post-treatment. Despite their efficacy, CAR T-cell therapies present unique challenges in preclinical safety assessment. The safety and pharmacokinetics of CAR T-cells are influenced by numerous factors including donor and recipient characteristics, product design, and manufacturing processes that are not well-predicted by existing in vitro and in vivo preclinical safety models. The CAR therapy-mediated toxicities in clinical settings primarily arise from unintended targeting of non-tumor cells, potential tumorigenicity, and severe immune activation syndromes like cytokine release syndrome and immune effector cell-associated neurotoxicity. Addressing these issues necessitates a deep understanding of CAR target expression in normal tissues, inclusive of the spatial microanatomical distribution, off-target screening, and a deep understanding CAR cell manufacturing practices and immunopathology. | [
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] | 0 | 10.1177/01926233241298570 | [
"Piersigilli",
"Carreira",
"Gervais",
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] | [
"Takeda Development Center Americas, Cambridge, MA, USA.",
"Johnson & Johnson Innovative Medicine, San Diego, CA, USA.",
"Charles River Laboratories, Evreux, France.",
"Novartis, Cambridge, MA, USA.",
"Labcorp, Madison, WI, USA.",
"Altos Labs, Redwood City, CA, USA."
] | [
"39644098"
] | [] | 8.459846 | 4.073452 |
39644077 | 152 | Ph- ALL: immunotherapy in upfront treatment. | Antibody-based and cell-based novel immunotherapies, such as bispecific T-cell engagers (BiTE), antibody-drug conjugates, or chimeric antigen receptor (CAR) T cells are currently standard treatment options for patients with relapsed or refractory (R/R) B-cell precursor acute lymphoblastic leukemia (ALL). To date, CD20-targeting monoclonal antibodies and the CD19-targeting BiTE's blinatumomab have been established elements of frontline therapy, either in patients with CD20+ ALL or in patients with measurable disease (MRD) following conventional chemotherapy. Recently, blinatumomab has also demonstrated a survival benefit in patients with MRD-negative ALL. Based on the observed high response rates and improved survival outcomes in patients with R/R ALL, antibody-based immunotherapies are being prospectively studied in the upfront setting, particularly in older adult patients, where even age-adapted conventional chemotherapies are still associated with significant rates of early death, treatment-related toxicity, and poor prognosis. In these approaches, conventional chemotherapy has been replaced or reduced and supplemented by immunotherapeutic agents, resulting in promising outcomes that form the basis for evaluating and defining new treatment standards. | [
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] | 2024-12-07 | 32 | 39644077 | [
"older adult patients",
"patients",
"conventional chemotherapy",
"T cells",
"standard treatment options",
"new treatment standards",
"significant rates",
"ALL",
"chimeric antigen receptor",
"immunotherapeutic agents",
"early death",
"outcomes",
"frontline therapy",
"antibody-based immunotherapies",
"BiTE",
"measurable disease",
"MRD",
"bispecific T-cell engagers",
"R/R ALL",
"CD20",
"poor prognosis",
"Antibody-based and cell-based novel immunotherapies",
"MRD-negative ALL",
"antibody-drug conjugates",
"the observed high response rates",
"CAR",
"elements",
"CD20-targeting monoclonal",
"relapsed or refractory (R/R) B-cell precursor acute lymphoblastic leukemia",
"even age-adapted conventional chemotherapies"
] | [] | 0 | 10.1182/hematology.2024000531 | [
"Stelljes"
] | [
"Department of Medicine A, Hematology and Oncology, University Hospital Münster, Münster, Germany."
] | [
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] | [] | 6.328296 | 6.514283 |
39644075 | 153 | T-cell-based therapies for treating relapsed or refractory mantle cell lymphoma. | While targeted therapies such as Bruton's tyrosine kinase and BCL2 inhibitors have fundamentally changed the treatment of mantle cell lymphoma (MCL), not all patients respond to these therapies, and responses are finite and can be fleeting, especially with high-risk MCL. As patients progress through successive therapies, the clinical course is characterized by shortening response times,1 frequent disease acceleration, and limited survival outcomes. Recently, the sensitivity of MCL to novel immune-based therapies is being realized with favorable results, as chimeric antigen receptor-modified T cells and bispecific T-cell-engaging antibodies are being investigated and implemented into practice for patients. However, critical issues remain to understand the role of these agents in routine practice. In this review, we discuss the current landscape regarding these agents, examine our approach to incorporating them into practice, and consider unanswered questions that we must ultimately address to improve outcomes for patients. | [
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"successive therapies",
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"patients",
"limited survival outcomes",
"practice",
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"response",
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"these therapies",
"the current landscape",
"the clinical course",
"these agents",
"not all patients",
"the role",
"our approach",
"the treatment"
] | [] | 0 | 10.1182/hematology.2024000657
10.1038/s41408-019-0209-5 | [
"Epstein-Peterson",
"Palomba"
] | [
"Lymphoma Service, Division of Hematologic Malignancies, New York, NY.\nCellular Therapy Service, Division of Hematologic Malignancies, Memorial Sloan Kettering Cancer Center, New York, NY.",
"Lymphoma Service, Division of Hematologic Malignancies, New York, NY.\nCellular Therapy Service, Division of Hematologic Malignancies, Memorial Sloan Kettering Cancer Center, New York, NY."
] | [
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39644060 | 154 | Relapsed/refractory CLL: the role of allo-SCT, CAR-T, and T-cell engagers. | Chronic lymphocytic leukemia (CLL) patients who are refractory to both Bruton's tyrosine kinase and B-cell/CLL lymphoma 2 (BCL2) inhibitors face a significant treatment challenge, with limited and short-lasting disease control options. This underscores the urgent need for novel therapeutic strategies. Immunotherapy has emerged as a promising approach to address this unmet need, offering the potential for durable remissions and improved patient outcomes. Historically, allogeneic stem cell transplantation has been used for high-risk CLL patients, demonstrating promising survival rates. However, its applicability is limited by high treatment-related mortality and chronic graft-versus-host disease, especially in older and frail patients. Chimeric antigen receptor (CAR) T-cell therapy is gaining attention for its potential in relapsed/refractory CLL. Early clinical trials have shown that CAR T cells can induce durable remissions, with encouraging overall response rates in heavily pretreated patients. Additionally, bispecific antibodies are being explored as immunotherapeutic strategies, showing promising preclinical and early clinical results in targeting CLL cells effectively. One of the major challenges in CLL treatment with T-cell-based therapies is the acquired T-cell dysfunction observed in patients. To overcome these limitations, strategies such as combining targeted agents with cellular immunotherapies, modifying CAR designs, and incorporating immunomodulatory compounds into the manufacturing process are being investigated. These innovative approaches aim to enhance T-cell engagement and improve outcomes for CLL patients, offering hope for more effective and sustainable treatments in the future. | [
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] | 2024-12-07 | 53 | 39644060 | [
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] | [] | 0 | 10.1182/hematology.2024000570 | [
"Kater",
"Siddiqi"
] | [
"Department of Hematology, Cancer Center Amsterdam, Amsterdam University Medical Centers, University of Amsterdam, Amsterdam, The Netherlands.",
"Department of Hematology/Hematopoietic Cell Transplantation, City of Hope Orange County, Irvine, CA."
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39643999 | 155 | Sequencing bispecific antibodies and CAR T cells for FL. | Treatment for relapsed/refractory (R/R) follicular lymphoma (FL) has evolved over recent years with the introduction of multiple novel immunotherapies: anti-CD3 × CD20 bispecific antibody (BsAb) T-cell engagers and anti-CD19 chimeric antigen receptor T cells (CAR T). Both drug classes are highly active, and their adverse event profiles overlap considerably, with cytokine release syndrome, cytopenias, and infections being most common. However, key differences include accessibility and logistical considerations as well as distinct neurologic toxicities, which make recommending a BsAb or CAR T a nuanced decision for each patient with R/R FL. Notably, patients could receive both classes of therapies in sequence; however, data guiding this decision are sparse. Considering the 3 most advanced agents in each class, we generally favor BsAbs before CAR T as the standard-of-care third-line treatment for the typical patient with R/R FL without concern for aggressive histologic transformation (HT). This is based on a 3-year follow-up of the mosunetuzumab phase 2 trial in R/R FL highlighting durable complete responses after a time-limited therapy with an acceptable safety profile for patients of all ages and reasonable performance status. We generally prioritize CAR T before BsAbs for patients with proven or suspected HT given the curative-potential of this approach based on trial data from R/R diffuse large B-cell lymphoma; it is unknown whether BsAbs offer the same long-term benefit in transformed FL. Overall, with the ability to personalize the sequencing of BsAbs and CAR T, the recently expanding portfolio of highly effective immunotherapies for R/R FL is poised to offer considerable benefit to this patient population. | [
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] | [] | 0 | 10.1182/hematology.2024000667 | [
"Russler-Germain",
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] | [
"Division of Oncology, Washington University School of Medicine, Siteman Cancer Center, St Louis, MO.",
"Division of Oncology, Washington University School of Medicine, Siteman Cancer Center, St Louis, MO."
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39643985 | 156 | Late complications and long-term care of adult CAR T-cell patients. | The success of chimeric antigen receptor (CAR) T-cell therapy in adult patients with hematologic malignancies has resulted in a large number of long-term survivors who may experience late complications distinct from those in the early CAR T-cell treatment period. These late complications, defined as occurring more than 90 days after CAR T-cell infusion, include cytopenias, infections, secondary malignancies, and delayed neurotoxicities. Late cytopenias may be from prolonged recovery after lymphodepleting (LD) chemotherapy or arise anew, raising concerns for recurrent primary disease or a secondary malignancy. Cytopenias are treated with supportive care, hematopoietic cytokines, and, occasionally, hematopoietic stem cell support. LD chemotherapy profoundly affects B, T, and natural killer cells. CD19 and B-cell maturation antigen are expressed on normal B cells and plasma cells, respectively, and the targeting of these structures by CAR T-cell products can result in prolonged lymphopenias and hypogammaglobulinemia, making infection an ongoing risk. Late infections are predominantly due to respiratory viruses, reactivation of herpes viruses, and Pneumocystis jirovecii. Patients may require ongoing prophylaxis and immunoglobulin replacement therapy. Although responses may be blunted, vaccinations are generally recommended for most adult CAR T-cell patients. Both hematologic and solid secondary malignancies are a known risk of CAR T-cell therapy; retroviruses used to produce CAR T-cell products have resulted in T-cell cancers secondary to insertional oncogenesis. It is essential to monitor for late complications in adult patients receiving CAR T-cells by using a multidisciplinary approach between referring hematologist oncologists and cell therapy centers to improve the outcomes and quality of life for these patients. | [
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] | [] | 0 | 10.1182/hematology.2024000534 | [
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"The David and Etta Jonas Center for Cellular Therapy, Section of Hematology/Oncology, Department of Medicine, University of Chicago, Chicago, IL."
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39643883 | 157 | Chimeric antigen receptor macrophages targeting c-MET(CAR-M-c-MET) inhibit pancreatic cancer progression and improve cytotoxic chemotherapeutic efficacy. | Pancreatic ductal adenocarcinoma (PDAC) is one of the most malignant tumors. Macrophages are abundant in the tumor microenvironment, making them an attractive target for therapeutic intervention. While current immunotherapies, including immune checkpoint inhibition (ICI) and chimeric antigen receptor T (CAR-T) cells, have shown limited efficacy in pancreatic cancer, a novel approach involving chimeric antigen receptor macrophages (CAR-M) has, although promising, not been explored in pancreatic cancer. In this study, we first investigated the role of CAR-M cells targeting c-MET in pancreatic cancer.
The effectiveness and rationality of c-MET as a target for CAR-M in pancreatic cancer were validated through bioinformatic analyses and immunohistochemical staining of samples from pancreatic cancer patients. We utilized flow cytometry and bioluminescence detection methods to demonstrate the specific binding and phagocytic killing effect of CAR-M on pancreatic cancer cells. Additionally, we observed the process of CAR-M engulfing pancreatic cancer cells using confocal microscopy and a long-term fluorescence live cell imaging system. In an in situ tumor model transplanted into NOD/SCID mice, we administered intraperitoneal injections of CAR-M to confirm its inhibitory function on pancreatic cancer. Furthermore, we validated these findings in human monocyte-derived macrophages (hMDM).
Bioinformatics and tumor tissue microarray analyses revealed significantly higher expression levels of c-MET in tumor tissues, compared to the paired peritumoral tissues, and higher c-MET expression correlated with worse patient survival. CAR-M cells were engineered using human monocytic THP-1 cell line and hMDM targeting c-MET (CAR-M-c-MET). The CAR-M-c-MET cells demonstrated highly specific binding to pancreatic cancer cells and exhibited more phagocytosis and killing abilities than the pro-inflammatory polarized control macrophages. In addition, CAR-M-c-MET cells synergized with various cytotoxic chemotherapeutic drugs. In a NOD/SCID murine model, intraperitoneally injected CAR-M-c-MET cells rapidly migrated to tumor tissue and substantially inhibited tumor growth, which did not lead to obvious side effects. Cytokine arrays and mRNA sequencing showed that CAR-M-c-MET produced higher levels of immune activators than control macrophages.
This study provides compelling evidence for the safety and efficacy of CAR-M therapy in treating pancreatic cancer. The results demonstrate that CAR-M-c-MET significantly suppresses pancreatic cancer progression and enhances the effectiveness of cytotoxic chemotherapy. Remarkably, no discernible side effects occur. Further clinical trials are warranted in human pancreatic cancer patients. | [
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] | 2024-12-07 | 36 | 39643883 | [
"pancreatic cancer cells",
"pancreatic cancer",
"pancreatic cancer progression",
"pancreatic cancer patients",
"human pancreatic cancer patients",
"CAR-M engulfing pancreatic cancer cells",
"Pancreatic ductal adenocarcinoma",
"human monocytic THP-1 cell line",
"CAR-M cells",
"tumor tissue",
"tumor tissues",
"chimeric antigen receptor macrophages",
"CAR-M",
"control macrophages",
"higher c-MET expression",
"CAR-M-c-MET cells",
"higher levels",
"immune checkpoint inhibition",
"obvious side effects",
"CAR-M therapy",
"antigen receptor",
"Macrophages",
"intraperitoneally injected CAR-M-c-MET cells",
"various cytotoxic chemotherapeutic drugs",
"CAR-M-c-MET",
"immune activators",
"Bioinformatics and tumor tissue microarray analyses",
"c-MET",
"bioinformatic analyses",
"limited efficacy"
] | [
"Chemotherapy",
"Chimeric antigen receptor macrophage",
"Pancreatic cancer",
"c-MET"
] | 0 | 10.1186/s12943-024-02184-8 | [
"Zheng",
"Yang",
"Huang",
"Yuan",
"Li",
"Liu",
"Jiang",
"Wu",
"Ju",
"Kleeff",
"Yin",
"Liao",
"Liu",
"Zhao"
] | [
"Department of General Surgery, State Key Laboratory of Complex Severe and Rare Diseases, Dongcheng District, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, No.1 Shuai Fu Yuan, Beijing, 100730, China.",
"Applied Biology Laboratory, College of Pharmaceutical and Biological Engineering, Shenyang University of Chemical Technology, Shenyang, 110142, China.",
"Department of General Surgery, State Key Laboratory of Complex Severe and Rare Diseases, Dongcheng District, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, No.1 Shuai Fu Yuan, Beijing, 100730, China.",
"Department of General Surgery, State Key Laboratory of Complex Severe and Rare Diseases, Dongcheng District, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, No.1 Shuai Fu Yuan, Beijing, 100730, China.",
"Department of General Surgery, State Key Laboratory of Complex Severe and Rare Diseases, Dongcheng District, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, No.1 Shuai Fu Yuan, Beijing, 100730, China.",
"Medical Research Center, State Key Laboratory of Complex Severe and Rare Diseases, Dongcheng District, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, No.1 Shuai Fu Yuan, Beijing, 100730, China.",
"Applied Biology Laboratory, College of Pharmaceutical and Biological Engineering, Shenyang University of Chemical Technology, Shenyang, 110142, China.",
"Applied Biology Laboratory, College of Pharmaceutical and Biological Engineering, Shenyang University of Chemical Technology, Shenyang, 110142, China.",
"Roc Rock Biotechnology (Shenzhen), Shenzhen, 518118, China.",
"Department of Visceral, Vascular and Endocrine Surgery, Martin-Luther-University Halle-Wittenberg, 06120, Halle (Saale), Germany.",
"Applied Biology Laboratory, College of Pharmaceutical and Biological Engineering, Shenyang University of Chemical Technology, Shenyang, 110142, China. [email protected].\nRoc Rock Biotechnology (Shenzhen), Shenzhen, 518118, China. [email protected].",
"Department of General Surgery, State Key Laboratory of Complex Severe and Rare Diseases, Dongcheng District, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, No.1 Shuai Fu Yuan, Beijing, 100730, China. [email protected].",
"Department of General Surgery, State Key Laboratory of Complex Severe and Rare Diseases, Dongcheng District, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, No.1 Shuai Fu Yuan, Beijing, 100730, China. [email protected].",
"Department of General Surgery, State Key Laboratory of Complex Severe and Rare Diseases, Dongcheng District, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, No.1 Shuai Fu Yuan, Beijing, 100730, China. [email protected]."
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] | [] | 10.227815 | 5.553867 |
39643037 | 158 | Exploring the potential of CAR-macrophage therapy. | Chimeric antigen receptor T cell (CAR-T) cell therapy has achieved significant success in treating hematologic malignancies, but its efficacy in solid tumor treatment is relatively limited. Therefore, researchers are exploring other genetically modified immune cells as potential treatment strategies to address the challenges in solid tumor therapy. Chimeric antigen receptor macrophage (CAR-M) involves the genetic engineering of macrophages to express chimeric antigen receptors, enabling them to recognize and attack tumor cells. In contrast to CAR-T cells, CAR-M cells offer distinct advantages such as enhanced infiltration and survival capabilities, along with a diverse array of anti-tumor mechanisms, making them a promising immunotherapy approach that may yield better results in solid tumor treatment. This article provides an overview of the research advancements in CAR-M-mediated tumor immunotherapy, encompassing topics such as the design and transduction of CAR, cell sources, anti-tumor mechanisms and clinical applications. The future research direction in this field will involve leveraging innovative biological technologies to augment the anti-tumor efficacy of CAR-M, understand the underlying mechanisms, and enhance the safety and efficacy of CAR-M therapy. | [
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] | 2024-12-07 | 1 | 39643037 | [
"tumor cells",
"anti-tumor mechanisms",
"Chimeric antigen receptor T cell",
"solid tumor treatment",
"solid tumor therapy",
"CAR",
"cell sources",
"Chimeric antigen receptor macrophage",
"chimeric antigen receptors",
"CAR-M cells",
"potential treatment strategies",
"the anti-tumor efficacy",
"efficacy",
"innovative biological technologies",
"CAR-M-mediated tumor immunotherapy",
"other genetically modified immune cells",
"CAR-M",
"CAR-M therapy",
"CAR-T) cell therapy",
"significant success",
"hematologic malignancies",
"better results",
"distinct advantages",
"CAR-T cells",
"macrophages",
"enhanced infiltration and survival capabilities",
"clinical applications",
"topics",
"transduction",
"The future research direction"
] | [
"CAR-M",
"Chimeric antigen receptor",
"Macrophage",
"Tumor immunotherapy"
] | 0 | 10.1016/j.lfs.2024.123300 | [
"Shi",
"Li",
"Dong",
"Yuan",
"Wang",
"Yang"
] | [
"Department of Immunology and Shandong Key Laboratory of Infection and Immunity, School of Basic Medical Sciences, Cheeloo College of Medicine, Shandong University, China. Electronic address: [email protected].",
"Department of Internal Medicine, Jinan No. 1 People's Hospital, China.",
"Department of Immunology and Shandong Key Laboratory of Infection and Immunity, School of Basic Medical Sciences, Cheeloo College of Medicine, Shandong University, China.",
"Department of Immunology and Shandong Key Laboratory of Infection and Immunity, School of Basic Medical Sciences, Cheeloo College of Medicine, Shandong University, China.",
"Department of Immunology and Shandong Key Laboratory of Infection and Immunity, School of Basic Medical Sciences, Cheeloo College of Medicine, Shandong University, China.",
"Department of Immunology and Shandong Key Laboratory of Infection and Immunity, School of Basic Medical Sciences, Cheeloo College of Medicine, Shandong University, China."
] | [
"39643037"
] | [] | 10.233029 | 5.370287 |
39642889 | 159 | EZH2 inhibition enhances T cell immunotherapies by inducing lymphoma immunogenicity and improving T cell function. | T cell-based immunotherapies have demonstrated effectiveness in treating diffuse large B cell lymphoma (DLBCL) and follicular lymphoma (FL) but predicting response and understanding resistance remains a challenge. To address this, we developed syngeneic models reflecting the genetics, epigenetics, and immunology of human FL and DLBCL. We show that EZH2 inhibitors reprogram these models to re-express T cell engagement genes and render them highly immunogenic. EZH2 inhibitors do not harm tumor-controlling T cells or CAR-T cells. Instead, they reduce regulatory T cells, promote memory chimeric antigen receptor (CAR) CD8 phenotypes, and reduce exhaustion, resulting in a decreased tumor burden. Intravital 2-photon imaging shows increased CAR-T recruitment and interaction within the tumor microenvironment, improving lymphoma cell killing. Therefore, EZH2 inhibition enhances CAR-T cell efficacy through direct effects on CAR-T cells, in addition to rendering lymphoma B cells immunogenic. This approach is currently being evaluated in two clinical trials, NCT05934838 and NCT05994235, to improve immunotherapy outcomes in B cell lymphoma patients. | [
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10.1038/nature13803 | [
"Isshiki",
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"Xia",
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"Division of Hematology/Oncology, Department of Medicine, Weill Cornell Medicine, Cornell University, New York, NY, USA.",
"Division of Hematology/Oncology, Department of Medicine, Weill Cornell Medicine, Cornell University, New York, NY, USA.",
"Division of Hematology/Oncology, Department of Medicine, Weill Cornell Medicine, Cornell University, New York, NY, USA; Institute for Computational Biomedicine, Weill Cornell Medicine, Cornell University, New York, NY, USA.",
"Division of Hematology/Oncology, Department of Medicine, Weill Cornell Medicine, Cornell University, New York, NY, USA.",
"Division of Hematology/Oncology, Department of Medicine, Weill Cornell Medicine, Cornell University, New York, NY, USA.",
"Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA.",
"Institute for Computational Biomedicine, Weill Cornell Medicine, Cornell University, New York, NY, USA; Department of Physiology and Biophysics, Weill Cornell Medicine, Cornell University, New York, NY, USA.",
"Division of Hematology/Oncology, Department of Medicine, Weill Cornell Medicine, Cornell University, New York, NY, USA.",
"Division of Hematology/Oncology, Department of Medicine, Weill Cornell Medicine, Cornell University, New York, NY, USA.",
"Division of Hematology/Oncology, Department of Medicine, Weill Cornell Medicine, Cornell University, New York, NY, USA.",
"Division of Hematology/Oncology, Department of Medicine, Weill Cornell Medicine, Cornell University, New York, NY, USA.",
"Department of Pathology and Laboratory Medicine, Weill Cornell Medicine, New York City, NY, USA; Laboratory of Comparative Pathology, Memorial Sloan Kettering Cancer Center, Weill Cornell Medicine, and Rockefeller University, New York City, NY, USA.",
"Department of Pathology and Laboratory Medicine, Weill Cornell Medicine, New York City, NY, USA.",
"Division of Hematology/Oncology, Department of Medicine, Weill Cornell Medicine, Cornell University, New York, NY, USA.",
"Division of Hematology/Oncology, Department of Medicine, Weill Cornell Medicine, Cornell University, New York, NY, USA.",
"Department of Immunology and Regenerative Biology, Weizmann Institute of Science, Rehovot 76100, Israel.",
"Department of Immunology and Regenerative Biology, Weizmann Institute of Science, Rehovot 76100, Israel.",
"Division of Hematology and Oncology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.",
"Division of Hematology and Oncology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.",
"Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA; Roswell Park Comprehensive Cancer Center, Buffalo, NY, USA.",
"Department of Pathology and Laboratory Medicine, Weill Cornell Medicine, New York City, NY, USA.",
"Division of Hematology/Oncology, Department of Medicine, Weill Cornell Medicine, Cornell University, New York, NY, USA.",
"Department of Pathology and Laboratory Medicine, Weill Cornell Medicine, New York City, NY, USA.",
"Division of Hematology/Oncology, Department of Medicine, Weill Cornell Medicine, Cornell University, New York, NY, USA.",
"Division of Hematology/Oncology, Department of Medicine, Weill Cornell Medicine, Cornell University, New York, NY, USA. Electronic address: [email protected]."
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39640015 | 160 | First-in-class transactivator-free, doxycycline-inducible IL-18-engineered CAR-T cells for relapsed/refractory B cell lymphomas. | Although chimeric antigen receptor (CAR) T cell therapy has revolutionized type B cancer treatment, efficacy remains limited in various lymphomas and solid tumors. Reinforcing conventional CAR-T cells to release cytokines can improve their efficacy but also increase safety concerns. Several strategies have been developed to regulate their secretion using minimal promoters that are controlled by chimeric proteins harboring transactivators. However, these chimeric proteins can disrupt the normal physiology of T cells. Here, we present the first transactivator-free anti-CD19 CAR-T cells able to control IL-18 expression (iTRUCK19.18) under ultra-low doses of doxycycline and without altering cellular fitness. Interestingly, IL-18 secretion requires T cell activation in addition to doxycycline, allowing the external regulation of CAR-T cell potency. This effect was translated into an increased CAR-T cell antitumor activity against aggressive hematologic and solid tumor models. In a clinically relevant context, we generated patient-derived iTRUCK19.18 cells capable of eradicating primary B cells tumors in a doxycycline-dependent manner. Furthermore, IL-18-releasing CAR-T cells polarized pro-tumoral macrophages toward an antitumoral phenotype, suggesting potential for modulating the tumor microenvironment. In summary, we showed that our platform can generate exogenously controlled CAR-T cells with enhanced potency and in the absence of transactivators. | [
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] | 2024-12-06 | 57 | 39640015 | [
"primary B cells tumors",
"conventional CAR-T cells",
"T cell activation",
"solid tumors",
"ultra-low doses",
"pro-tumoral macrophages",
"solid tumor models",
"T cells",
"CAR-T cell potency",
"type B cancer treatment",
"an increased CAR-T cell antitumor activity",
"exogenously controlled CAR-T cells",
"patient-derived iTRUCK19.18 cells",
"IL-18-releasing CAR-T cells",
"CAR) T cell therapy",
"the first transactivator-free anti-CD19 CAR-T cells",
"chimeric proteins",
"efficacy",
"enhanced potency",
"doxycycline",
"minimal promoters",
"aggressive hematologic",
"transactivators",
"various lymphomas",
"chimeric antigen receptor",
"Several strategies",
"cellular fitness",
"safety concerns",
"potential",
"iTRUCK19.18"
] | [
"CAR-T cells",
"IL-18",
"Lent-On-Plus",
"MT: Delivery Strategies",
"TRUCKs",
"animal models",
"doxycycline",
"lentiviral vectors",
"lymphoma",
"regulation"
] | 0 | 10.1016/j.omtn.2024.102308 | [
"Justicia-Lirio",
"Tristán-Manzano",
"Maldonado-Pérez",
"Barbero-Jiménez",
"Cortijo-Gutiérrez",
"Pavlovic",
"Molina-Estevez",
"Muñoz",
"Hinckley-Boned",
"Rodriguez-Madoz",
"Prosper",
"Griñán-Lison",
"Navarro-Marchal",
"Panisello",
"Muñoz-Ballester",
"González-Sierra",
"Herrera",
"Marchal",
"Martín"
] | [
"LentiStem Biotech, Pfizer-University of Granada-Andalusian Regional Government Centre for Genomics and Oncological Research (GENYO), PTS, Av. de la Ilustración 114, 18016 Granada, Spain.",
"LentiStem Biotech, Pfizer-University of Granada-Andalusian Regional Government Centre for Genomics and Oncological Research (GENYO), PTS, Av. de la Ilustración 114, 18016 Granada, Spain.",
"Department of Biochemistry and Molecular Biology III and Immunology, Faculty of Medicine, University of Granada, Av. de la Investigación, 11, 18006 Granada, Spain.\nDepartment of Genomic Medicine, Pfizer-University of Granada-Andalusian Regional Government Centre for Genomics and Oncological Research (GENYO), PTS, Av. de la Ilustración 114, 18016 Granada, Spain.",
"LentiStem Biotech, Pfizer-University of Granada-Andalusian Regional Government Centre for Genomics and Oncological Research (GENYO), PTS, Av. de la Ilustración 114, 18016 Granada, Spain.",
"Department of Genomic Medicine, Pfizer-University of Granada-Andalusian Regional Government Centre for Genomics and Oncological Research (GENYO), PTS, Av. de la Ilustración 114, 18016 Granada, Spain.",
"Department of Genomic Medicine, Pfizer-University of Granada-Andalusian Regional Government Centre for Genomics and Oncological Research (GENYO), PTS, Av. de la Ilustración 114, 18016 Granada, Spain.\nMaimonides Institute of Biomedical Research in Cordoba (IMIBIC), Cellular Therapy Unit, Reina Sofía University Hospital, University of Cordoba, Av. Menéndez Pidal, 14004 Cordoba, Spain.",
"Department of Genomic Medicine, Pfizer-University of Granada-Andalusian Regional Government Centre for Genomics and Oncological Research (GENYO), PTS, Av. de la Ilustración 114, 18016 Granada, Spain.\nInstituto de Investigación Biosanitaria ibs.GRANADA, University Hospitals of Granada, University of Granada, Av. de Madrid 15, 18012 Granada, Spain.",
"Department of Genomic Medicine, Pfizer-University of Granada-Andalusian Regional Government Centre for Genomics and Oncological Research (GENYO), PTS, Av. de la Ilustración 114, 18016 Granada, Spain.\nInstituto de Investigación Biosanitaria ibs.GRANADA, University Hospitals of Granada, University of Granada, Av. de Madrid 15, 18012 Granada, Spain.\nDepartment of Cellular Biology, Faculty of Sciences, University of Granada, Av. de Fuente Nueva, 18071 Granada, Spain.",
"Department of Genomic Medicine, Pfizer-University of Granada-Andalusian Regional Government Centre for Genomics and Oncological Research (GENYO), PTS, Av. de la Ilustración 114, 18016 Granada, Spain.",
"Centro de Investigacion Biomedica en Red de Cancer (CIBERONC), Madrid, Spain.\nHemato-Oncology Program, Cima Universidad de Navarra, IdiSNA, Pamplona, Spain.\nCancer Center Clinica Universidad de Navarra (CCUN), Pamplona, Spain.",
"Centro de Investigacion Biomedica en Red de Cancer (CIBERONC), Madrid, Spain.\nHemato-Oncology Program, Cima Universidad de Navarra, IdiSNA, Pamplona, Spain.\nCancer Center Clinica Universidad de Navarra (CCUN), Pamplona, Spain.\nHematology and Cell Therapy Department, Clinica Universidad de Navarra, IdiSNA, Pamplona, Spain.",
"Instituto de Investigación Biosanitaria ibs.GRANADA, University Hospitals of Granada, University of Granada, Av. de Madrid 15, 18012 Granada, Spain.\nExcellence Research Unit \"Modeling Nature\" (MNat), University of Granada, 18016 Granada, Spain.\nBiopathology and Regenerative Medicine Institute (IBIMER), Centre for Biomedical Research (CIBM), University of Granada, 18016 Granada, Spain.\nDepartment of Biochemistry and Molecular Biology II, Faculty of Pharmacy, University of Granada, 18071 Granada, Spain.",
"Instituto de Investigación Biosanitaria ibs.GRANADA, University Hospitals of Granada, University of Granada, Av. de Madrid 15, 18012 Granada, Spain.\nExcellence Research Unit \"Modeling Nature\" (MNat), University of Granada, 18016 Granada, Spain.\nBiopathology and Regenerative Medicine Institute (IBIMER), Centre for Biomedical Research (CIBM), University of Granada, 18016 Granada, Spain.\nCancer Research UK Edinburgh Centre, Institute of Genetics and Cancer, University of Edinburgh, Edinburgh EH4 2XU, UK.",
"Josep Carreras Leukemia Research Institute, Barcelona, Spain.\nGermans Trias i Pujol Research Institute (IGTP), Badalona, Spain.\nRed Española de Terapias Avanzadas (TERAV)-Instituto de Salud Carlos III (ISCIII), Madrid, Spain.",
"Instituto de Investigación Biosanitaria ibs.GRANADA, University Hospitals of Granada, University of Granada, Av. de Madrid 15, 18012 Granada, Spain.\nHematology and Hemotherapy Unit, Virgen de las Nieves University Hospital, Av. de las Fuerzas Armadas 2, 18014 Granada, Spain.",
"Instituto de Investigación Biosanitaria ibs.GRANADA, University Hospitals of Granada, University of Granada, Av. de Madrid 15, 18012 Granada, Spain.\nHematology and Hemotherapy Unit, Virgen de las Nieves University Hospital, Av. de las Fuerzas Armadas 2, 18014 Granada, Spain.",
"Maimonides Institute of Biomedical Research in Cordoba (IMIBIC), Cellular Therapy Unit, Reina Sofía University Hospital, University of Cordoba, Av. Menéndez Pidal, 14004 Cordoba, Spain.",
"Instituto de Investigación Biosanitaria ibs.GRANADA, University Hospitals of Granada, University of Granada, Av. de Madrid 15, 18012 Granada, Spain.\nExcellence Research Unit \"Modeling Nature\" (MNat), University of Granada, 18016 Granada, Spain.\nBiopathology and Regenerative Medicine Institute (IBIMER), Centre for Biomedical Research (CIBM), University of Granada, 18016 Granada, Spain.\nDepartment of Human Anatomy and Embryology, Faculty of Medicine, University of Granada, Av. de la Investigación 11, 18006 Granada, Spain.",
"Department of Biochemistry and Molecular Biology III and Immunology, Faculty of Medicine, University of Granada, Av. de la Investigación, 11, 18006 Granada, Spain.\nDepartment of Genomic Medicine, Pfizer-University of Granada-Andalusian Regional Government Centre for Genomics and Oncological Research (GENYO), PTS, Av. de la Ilustración 114, 18016 Granada, Spain.\nInstituto de Investigación Biosanitaria ibs.GRANADA, University Hospitals of Granada, University of Granada, Av. de Madrid 15, 18012 Granada, Spain.\nExcellence Research Unit \"Modeling Nature\" (MNat), University of Granada, 18016 Granada, Spain."
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] | [] | 7.870746 | 5.241285 |
39637860 | 161 | Modulation of TCR stimulation and pifithrin-α improve the genomic safety profile of CRISPR-engineered human T cells. | CRISPR-engineered chimeric antigen receptor (CAR) T cells are at the forefront of novel cancer treatments. However, several reports describe the occurrence of CRISPR-induced chromosomal aberrations. So far, measures to increase the genomic safety of T cell products focused mainly on the components of the CRISPR-Cas9 system and less on T cell-intrinsic features, such as their massive expansion after T cell receptor (TCR) stimulation. Here, we describe driving forces of indel formation in primary human T cells. Increased T cell activation and proliferation speed correlate with larger deletions. Editing of non-activated T cells reduces the risk of large deletions with the downside of reduced knockout efficiencies. Alternatively, the addition of the small-molecule pifithrin-α limits large deletions, chromosomal translocations, and aneuploidy in a p53-independent manner while maintaining the functionality of CRISPR-engineered T cells, including CAR T cells. Controlling T cell activation and pifithrin-α treatment are easily implementable strategies to improve the genomic integrity of CRISPR-engineered T cells. | [
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] | [
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10.3389/fgeed.2023.1130736 | [
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] | [
"Technical University of Munich (TUM), School of Medicine and Health, Department of Preclinical Medicine, Institute for Medical Microbiology, Immunology and Hygiene, 81675 Munich, Germany.",
"Technical University of Munich (TUM), School of Medicine and Health, Department of Preclinical Medicine, Institute for Medical Microbiology, Immunology and Hygiene, 81675 Munich, Germany.",
"Technical University of Munich (TUM), School of Medicine and Health, Department of Preclinical Medicine, Institute for Medical Microbiology, Immunology and Hygiene, 81675 Munich, Germany.",
"Institute for Transfusion Medicine and Gene Therapy, Medical Center - University of Freiburg, 79106 Freiburg, Germany; Center for Chronic Immunodeficiency (CCI), Medical Center - University of Freiburg, 79106 Freiburg, Germany.",
"Technical University of Munich (TUM), School of Medicine and Health, Department of Preclinical Medicine, Institute for Medical Microbiology, Immunology and Hygiene, 81675 Munich, Germany.",
"Technical University of Munich (TUM), School of Medicine and Health, Department of Preclinical Medicine, Institute for Medical Microbiology, Immunology and Hygiene, 81675 Munich, Germany.",
"Technical University of Munich (TUM), School of Medicine and Health, Department of Preclinical Medicine, Institute for Medical Microbiology, Immunology and Hygiene, 81675 Munich, Germany.",
"Institute of Medical Bioinformatics and Systems Medicine, Medical Center - University of Freiburg, Freiburg, Germany; Faculty of Medicine, University of Freiburg, 79106 Freiburg, Germany.",
"Core Facility Statistical Consulting, Helmholtz Zentrum München, 85764 Neuherberg, Germany.",
"Core Facility Statistical Consulting, Helmholtz Zentrum München, 85764 Neuherberg, Germany.",
"Institute of Computational Biology, Helmholtz Zentrum München, 85764 Neuherberg, Germany; School of Computing, Information and Technology, Technical University of Munich, 85748 Garching, Germany.",
"Institute of Medical Bioinformatics and Systems Medicine, Medical Center - University of Freiburg, Freiburg, Germany; Faculty of Medicine, University of Freiburg, 79106 Freiburg, Germany; German Cancer Consortium (DKTK), Partner site Freiburg, a partnership between DKFZ and Medical Center - University of Freiburg, 79106 Freiburg, Germany.",
"Technical University of Munich (TUM), School of Medicine and Health, Department of Preclinical Medicine, Institute for Medical Microbiology, Immunology and Hygiene, 81675 Munich, Germany; German Center for Infection Research, Deutsches Zentrum für Infektionsforschung (DZIF), Partner Site Munich, 81675 Munich, Germany.",
"Institute for Transfusion Medicine and Gene Therapy, Medical Center - University of Freiburg, 79106 Freiburg, Germany; Center for Chronic Immunodeficiency (CCI), Medical Center - University of Freiburg, 79106 Freiburg, Germany; Faculty of Medicine, University of Freiburg, 79106 Freiburg, Germany.",
"Technical University of Munich (TUM), School of Medicine and Health, Department of Preclinical Medicine, Institute for Medical Microbiology, Immunology and Hygiene, 81675 Munich, Germany; TUM, Institute for Advanced Study, 85748 Garching, Germany. Electronic address: [email protected]."
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39637858 | 162 | CD97 maintains tumorigenicity of glioblastoma stem cells via mTORC2 signaling and is targeted by CAR Th9 cells. | Glioblastoma (GBM) stem cells (GSCs) contribute to poor prognosis in patients with GBM. Identifying molecular markers is crucial for developing targeted therapies. Here, we identify cluster of differentiation 97 (CD97) as an optimal GSC surface antigen for potential targeting by chimeric antigen receptor (CAR) T cell therapy through in vitro antibody screening. CD97 is consistently expressed in all validated patient-derived GSCs and positively correlated with known intracellular GSC markers. Silencing CD97 reduces GSC tumorigenicity-related activities, including self-renewal, proliferation, and tumor progression. Transcriptome analysis reveals that CD97 activates mTORC2, leading to AKT S473 phosphorylation and enhanced expression of the downstream genes ARHGAP1, BZW1, and BZW2. Inhibiting mTORC2 with JR-AB2-011 suppresses GSC tumorigenicity and downstream gene expression. We develop CD97-CAR T helper (Th) 9 cells, which exhibit potent cytotoxic effects in vitro and extend survival in mice. These findings suggest that CD97 is a promising GSC-enriched antigen and that targeting it with CAR Th9 cells offers a potential therapeutic strategy for GBM. | [
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] | 2024-12-06 | 86 | 39637858 | [
"GSC tumorigenicity",
"known intracellular GSC markers",
"Silencing CD97",
"CD97",
"GSC",
"downstream gene expression",
"chimeric antigen receptor",
"potent cytotoxic effects",
"targeted therapies",
"AKT S473 phosphorylation",
"CD97-CAR T helper",
"an optimal GSC surface antigen",
"GSC tumorigenicity-related activities",
"enhanced expression",
"AKT S473",
"molecular markers",
"poor prognosis",
"mTORC2",
"GBM",
"CAR",
"patients",
"potential targeting",
"tumor progression",
"CAR Th9 cells",
"Transcriptome analysis",
"a promising GSC-enriched antigen",
"proliferation",
"GSCs",
"ARHGAP1",
"survival"
] | [
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10.1158/1541-7786.Mcr-08-0435 | [
"Zhou",
"Lin",
"Jin",
"Niu",
"Yuan",
"Chai",
"Zhang",
"Guo",
"Kim",
"Liu",
"Deng",
"Park",
"Choi",
"Shi",
"Yin"
] | [
"The Zhongzhou Laboratory for Integrative Biology, Henan Key Laboratory of Brain Targeted Bio-Nanomedicine, School of Life Sciences, Henan University, Kaifeng, Henan 475004, China; Henan-Macquarie University Joint Centre for Biomedical Innovation, School of Life Sciences, Henan University, Kaifeng, Henan 475004, China.",
"Henan Institute of Medical and Pharmaceutical Sciences, Zhengzhou University, Zhengzhou, Henan 450052, China; Research Institute, National Cancer Center, Goyang, Gyeonggi 10408, Republic of Korea.",
"The Zhongzhou Laboratory for Integrative Biology, Henan Key Laboratory of Brain Targeted Bio-Nanomedicine, School of Life Sciences, Henan University, Kaifeng, Henan 475004, China; School of Pharmacy, Henan University, Kaifeng, Henan 475004, China.",
"The Zhongzhou Laboratory for Integrative Biology, Henan Key Laboratory of Brain Targeted Bio-Nanomedicine, School of Life Sciences, Henan University, Kaifeng, Henan 475004, China; Henan-Macquarie University Joint Centre for Biomedical Innovation, School of Life Sciences, Henan University, Kaifeng, Henan 475004, China.",
"The Zhongzhou Laboratory for Integrative Biology, Henan Key Laboratory of Brain Targeted Bio-Nanomedicine, School of Life Sciences, Henan University, Kaifeng, Henan 475004, China; Henan-Macquarie University Joint Centre for Biomedical Innovation, School of Life Sciences, Henan University, Kaifeng, Henan 475004, China.",
"The Zhongzhou Laboratory for Integrative Biology, Henan Key Laboratory of Brain Targeted Bio-Nanomedicine, School of Life Sciences, Henan University, Kaifeng, Henan 475004, China; Henan-Macquarie University Joint Centre for Biomedical Innovation, School of Life Sciences, Henan University, Kaifeng, Henan 475004, China; Cancer Biomedical Science, Graduate School of Cancer Science and Policy, National Cancer Center, Goyang 10408, Republic of Korea.",
"The Zhongzhou Laboratory for Integrative Biology, Henan Key Laboratory of Brain Targeted Bio-Nanomedicine, School of Life Sciences, Henan University, Kaifeng, Henan 475004, China; Henan-Macquarie University Joint Centre for Biomedical Innovation, School of Life Sciences, Henan University, Kaifeng, Henan 475004, China.",
"The Zhongzhou Laboratory for Integrative Biology, Henan Key Laboratory of Brain Targeted Bio-Nanomedicine, School of Life Sciences, Henan University, Kaifeng, Henan 475004, China; Henan-Macquarie University Joint Centre for Biomedical Innovation, School of Life Sciences, Henan University, Kaifeng, Henan 475004, China.",
"Cancer Biomedical Science, Graduate School of Cancer Science and Policy, National Cancer Center, Goyang 10408, Republic of Korea.",
"The Zhongzhou Laboratory for Integrative Biology, Henan Key Laboratory of Brain Targeted Bio-Nanomedicine, School of Life Sciences, Henan University, Kaifeng, Henan 475004, China; Henan-Macquarie University Joint Centre for Biomedical Innovation, School of Life Sciences, Henan University, Kaifeng, Henan 475004, China; Cancer Biomedical Science, Graduate School of Cancer Science and Policy, National Cancer Center, Goyang 10408, Republic of Korea.",
"The Zhongzhou Laboratory for Integrative Biology, Henan Key Laboratory of Brain Targeted Bio-Nanomedicine, School of Life Sciences, Henan University, Kaifeng, Henan 475004, China; Henan-Macquarie University Joint Centre for Biomedical Innovation, School of Life Sciences, Henan University, Kaifeng, Henan 475004, China; Cancer Biomedical Science, Graduate School of Cancer Science and Policy, National Cancer Center, Goyang 10408, Republic of Korea.",
"Research Institute, National Cancer Center, Goyang, Gyeonggi 10408, Republic of Korea; Cancer Biomedical Science, Graduate School of Cancer Science and Policy, National Cancer Center, Goyang 10408, Republic of Korea.",
"The Zhongzhou Laboratory for Integrative Biology, Henan Key Laboratory of Brain Targeted Bio-Nanomedicine, School of Life Sciences, Henan University, Kaifeng, Henan 475004, China; School of Pharmacy, Henan University, Kaifeng, Henan 475004, China. Electronic address: [email protected].",
"The Zhongzhou Laboratory for Integrative Biology, Henan Key Laboratory of Brain Targeted Bio-Nanomedicine, School of Life Sciences, Henan University, Kaifeng, Henan 475004, China; Henan-Macquarie University Joint Centre for Biomedical Innovation, School of Life Sciences, Henan University, Kaifeng, Henan 475004, China. Electronic address: [email protected].",
"The Zhongzhou Laboratory for Integrative Biology, Henan Key Laboratory of Brain Targeted Bio-Nanomedicine, School of Life Sciences, Henan University, Kaifeng, Henan 475004, China; Henan-Macquarie University Joint Centre for Biomedical Innovation, School of Life Sciences, Henan University, Kaifeng, Henan 475004, China. Electronic address: [email protected]."
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39636990 | 163 | Engineering synthetic suppressor T cells that execute locally targeted immunoprotective programs. | Immune homeostasis requires a balance of inflammatory and suppressive activities. To design cells potentially useful for local immune suppression, we engineered conventional CD4 | [
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"local immune suppression",
"Immune homeostasis",
"conventional CD4",
"cells",
"inflammatory and suppressive activities",
"a balance",
"we"
] | [] | 0 | 10.1126/science.adl4793 | [
"Reddy",
"Maachi",
"Xiao",
"Simic",
"Yu",
"Tonai",
"Cabanillas",
"Serrano-Wu",
"Pauerstein",
"Tamaki",
"Allen",
"Parent",
"Hebrok",
"Lim"
] | [
"UCSF Cell Design Institute, University of California, San Francisco, San Francisco, CA, USA.\nDepartment of Cellular and Molecular Pharmacology, University of California, San Francisco, San Francisco, CA, USA.",
"Diabetes Center, University of California, San Francisco, San Francisco, CA, USA.",
"UCSF Cell Design Institute, University of California, San Francisco, San Francisco, CA, USA.\nDepartment of Cellular and Molecular Pharmacology, University of California, San Francisco, San Francisco, CA, USA.\nDiabetes Center, University of California, San Francisco, San Francisco, CA, USA.",
"UCSF Cell Design Institute, University of California, San Francisco, San Francisco, CA, USA.\nDepartment of Cellular and Molecular Pharmacology, University of California, San Francisco, San Francisco, CA, USA.",
"UCSF Cell Design Institute, University of California, San Francisco, San Francisco, CA, USA.\nDepartment of Cellular and Molecular Pharmacology, University of California, San Francisco, San Francisco, CA, USA.",
"UCSF Cell Design Institute, University of California, San Francisco, San Francisco, CA, USA.\nDepartment of Cellular and Molecular Pharmacology, University of California, San Francisco, San Francisco, CA, USA.",
"UCSF Cell Design Institute, University of California, San Francisco, San Francisco, CA, USA.\nDepartment of Cellular and Molecular Pharmacology, University of California, San Francisco, San Francisco, CA, USA.",
"UCSF Cell Design Institute, University of California, San Francisco, San Francisco, CA, USA.\nDepartment of Cellular and Molecular Pharmacology, University of California, San Francisco, San Francisco, CA, USA.",
"UCSF Cell Design Institute, University of California, San Francisco, San Francisco, CA, USA.\nDepartment of Pediatrics, University of California, San Francisco, San Francisco, CA, USA.",
"UCSF CoLabs, University of California, San Francisco, San Francisco, CA, USA.",
"UCSF Cell Design Institute, University of California, San Francisco, San Francisco, CA, USA.\nParker Institute for Cancer Immunotherapy, University of California, San Francisco, San Francisco, CA, USA.\nHelen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, CA, USA.\nDepartment of Medicine, University of California San Francisco, San Francisco, CA, USA.",
"Diabetes Center, University of California, San Francisco, San Francisco, CA, USA.",
"Diabetes Center, University of California, San Francisco, San Francisco, CA, USA.",
"UCSF Cell Design Institute, University of California, San Francisco, San Francisco, CA, USA.\nDepartment of Cellular and Molecular Pharmacology, University of California, San Francisco, San Francisco, CA, USA.\nHelen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, CA, USA."
] | [
"39636990"
] | [] | 9.289474 | 4.174129 |
39636984 | 164 | Programming tissue-sensing T cells that deliver therapies to the brain. | To engineer cells that can specifically target the central nervous system (CNS), we identified extracellular CNS-specific antigens, including components of the CNS extracellular matrix and surface molecules expressed on neurons or glial cells. Synthetic Notch receptors engineered to detect these antigens were used to program T cells to induce the expression of diverse payloads only in the brain. CNS-targeted T cells that induced chimeric antigen receptor expression efficiently cleared primary and secondary brain tumors without harming cross-reactive cells outside of the brain. Conversely, CNS-targeted cells that locally delivered the immunosuppressive cytokine interleukin-10 ameliorated symptoms in a mouse model of neuroinflammation. Tissue-sensing cells represent a strategy for addressing diverse disorders in an anatomically targeted manner. | [
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] | 2024-12-05 | 1 | 39636984 | [
"T cells",
"cross-reactive cells",
"glial cells",
"cells",
"chimeric antigen receptor expression",
"CNS-targeted T cells",
"diverse disorders",
"Synthetic Notch receptors",
"diverse payloads",
"surface molecules",
"extracellular CNS-specific antigens",
"Tissue-sensing cells",
"CNS",
"symptoms",
"primary and secondary brain tumors",
"Synthetic Notch",
"interleukin-10",
"the CNS extracellular matrix",
"components",
"neurons",
"the central nervous system",
"neuroinflammation",
"Conversely, CNS-targeted cells",
"the immunosuppressive cytokine",
"a mouse model",
"these antigens",
"an anatomically targeted manner",
"the brain",
"the expression",
"a strategy"
] | [] | 0 | 10.1126/science.adl4237 | [
"Simic",
"Watchmaker",
"Gupta",
"Wang",
"Sagan",
"Duecker",
"Shepherd",
"Diebold",
"Pineo-Cavanaugh",
"Haegelin",
"Zhu",
"Ng",
"Yu",
"Tonai",
"Cardarelli",
"Reddy",
"Sidhu",
"Troyanskaya",
"Hauser",
"Wilson",
"Zamvil",
"Okada",
"Lim"
] | [
"UCSF Cell Design Institute and Department of Cellular & Molecular Pharmacology, University of California San Francisco, San Francisco, CA, USA.",
"Department of Neurological Surgery, University of California San Francisco, San Francisco, CA, USA.",
"Weill Institute for Neurosciences, Department of Neurology, University of California San Francisco, San Francisco, CA, USA.",
"Department of Computer Science, Princeton University, Princeton, NJ, USA.\nLewis-Sigler Institute of Integrative Genomics, Princeton University, Princeton, NJ, USA.",
"Weill Institute for Neurosciences, Department of Neurology, University of California San Francisco, San Francisco, CA, USA.",
"UCSF Cell Design Institute and Department of Cellular & Molecular Pharmacology, University of California San Francisco, San Francisco, CA, USA.",
"UCSF Cell Design Institute and Department of Cellular & Molecular Pharmacology, University of California San Francisco, San Francisco, CA, USA.",
"Department of Neurological Surgery, University of California San Francisco, San Francisco, CA, USA.",
"Department of Neurological Surgery, University of California San Francisco, San Francisco, CA, USA.",
"Department of Neurological Surgery, University of California San Francisco, San Francisco, CA, USA.",
"UCSF Cell Design Institute and Department of Cellular & Molecular Pharmacology, University of California San Francisco, San Francisco, CA, USA.",
"UCSF Cell Design Institute and Department of Cellular & Molecular Pharmacology, University of California San Francisco, San Francisco, CA, USA.",
"UCSF Cell Design Institute and Department of Cellular & Molecular Pharmacology, University of California San Francisco, San Francisco, CA, USA.",
"UCSF Cell Design Institute and Department of Cellular & Molecular Pharmacology, University of California San Francisco, San Francisco, CA, USA.",
"School of Pharmacy, University of Waterloo, Waterloo, Ontario, Canada.",
"UCSF Cell Design Institute and Department of Cellular & Molecular Pharmacology, University of California San Francisco, San Francisco, CA, USA.",
"School of Pharmacy, University of Waterloo, Waterloo, Ontario, Canada.",
"Department of Computer Science, Princeton University, Princeton, NJ, USA.\nLewis-Sigler Institute of Integrative Genomics, Princeton University, Princeton, NJ, USA.\nCenter for Computational Biology, Flatiron Institute, New York, NY, USA.",
"Weill Institute for Neurosciences, Department of Neurology, University of California San Francisco, San Francisco, CA, USA.",
"Weill Institute for Neurosciences, Department of Neurology, University of California San Francisco, San Francisco, CA, USA.",
"Weill Institute for Neurosciences, Department of Neurology, University of California San Francisco, San Francisco, CA, USA.\nProgram in Immunology, University of California San Francisco, San Francisco, CA, USA.",
"Department of Neurological Surgery, University of California San Francisco, San Francisco, CA, USA.\nParker Institute for Cancer Immunotherapy, San Francisco, CA, USA.\nHelen Diller Cancer Center, University of California San Francisco, San Francisco, CA, USA.",
"UCSF Cell Design Institute and Department of Cellular & Molecular Pharmacology, University of California San Francisco, San Francisco, CA, USA.\nParker Institute for Cancer Immunotherapy, San Francisco, CA, USA."
] | [
"39636984"
] | [] | 9.713594 | 4.637138 |
39632807 | 165 | Inhibition of furin in CAR macrophages directs them toward a proinflammatory phenotype and enhances their antitumor activities. | Chimeric antigen receptor (CAR)-T-cell therapy has revolutionized cellular immunotherapy, demonstrating remarkable efficacy in hematological cancers. However, its application in solid tumors faces significant challenges, including limited T-cell infiltration and tumor-induced immunosuppression. Given the prominent role of macrophages in the tumor microenvironment, their phenotypic plasticity and inherent antitumor properties, such as phagocytosis, offer a promising avenue for therapeutic intervention. This study focuses on the development of a second generation of CAR macrophages (CAR-Ms). We elucidated the role of the proprotein convertase furin in macrophages, demonstrating its overexpression in the presence of tumor cells. Importantly, furin inhibition maintains a proinflammatory macrophage phenotype, potentially redirecting them towards an antitumor state. Compared to furin-expressing counterparts, furin-inhibited CAR-Ms exhibited heightened antitumor phagocytic activity against breast cancer cells and ex vivo patient-derived tumoroids. Notably, they sustained a persistent proinflammatory profile, indicative of enhanced tumoricidal potential. Additionally, furin-inhibited CAR-Ms secreted factors that promote T-cell activation, offering a means to modulate the tumor microenvironment. In summary, our work highlights the translational potential of furin-inhibited CAR-Ms as a potent cellular therapy to mitigate macrophage exhaustion within the tumor environment. By capitalizing on macrophage-mediated antitumor responses, these findings pave the way for the development of second-generation CAR-M therapeutic strategies tailored for solid tumors. | [
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] | 2024-12-05 | 39 | 39632807 | [
"tumor cells",
"CAR macrophages",
"solid tumors",
"macrophage exhaustion",
"breast cancer cells",
"macrophages",
"heightened antitumor phagocytic activity",
"furin inhibition",
"inherent antitumor properties",
"enhanced tumoricidal potential",
"cellular immunotherapy",
"macrophage-mediated antitumor responses",
"limited T-cell infiltration",
"hematological cancers",
"therapeutic intervention",
"Chimeric antigen receptor",
"a proinflammatory macrophage phenotype",
"significant challenges",
"second",
"T-cell activation",
"CAR)-T-cell therapy",
"remarkable efficacy",
"furin-inhibited CAR-Ms",
"tumor-induced immunosuppression",
"the tumor microenvironment",
"second-generation CAR-M therapeutic strategies",
"the tumor environment",
"ex vivo patient-derived tumoroids",
"furin-expressing counterparts",
"a potent cellular therapy"
] | [] | 0 | 10.1038/s41419-024-07267-4 | [
"Ziane-Chaouche",
"Raffo-Romero",
"Hajjaji",
"Kobeissy",
"Pinheiro",
"Aboulouard",
"Cozzani",
"Mitra",
"Fournier",
"Cizkova",
"Salzet",
"Duhamel"
] | [
"Université Lille, Inserm, CHU Lille, U1192, Laboratoire Protéomique, Réponse Inflammatoire Et Spectrométrie de Masse (PRISM), Villeneuve d'Ascq, France.\nEquipe Labellisée Ligue Contre le Cancer, Villeneuve d'Ascq, France.",
"Université Lille, Inserm, CHU Lille, U1192, Laboratoire Protéomique, Réponse Inflammatoire Et Spectrométrie de Masse (PRISM), Villeneuve d'Ascq, France.\nEquipe Labellisée Ligue Contre le Cancer, Villeneuve d'Ascq, France.",
"Université Lille, Inserm, CHU Lille, U1192, Laboratoire Protéomique, Réponse Inflammatoire Et Spectrométrie de Masse (PRISM), Villeneuve d'Ascq, France.\nEquipe Labellisée Ligue Contre le Cancer, Villeneuve d'Ascq, France.\nBreast Cancer Unit, Oscar Lambret Center, Lille, France.",
"Department of Biochemistry and Molecular Genetics, Faculty of Medicine, American University of Beirut, Beirut, Lebanon.",
"Université Lille, Inserm, CHU Lille, U1192, Laboratoire Protéomique, Réponse Inflammatoire Et Spectrométrie de Masse (PRISM), Villeneuve d'Ascq, France.\nEquipe Labellisée Ligue Contre le Cancer, Villeneuve d'Ascq, France.",
"Université Lille, Inserm, CHU Lille, U1192, Laboratoire Protéomique, Réponse Inflammatoire Et Spectrométrie de Masse (PRISM), Villeneuve d'Ascq, France.\nEquipe Labellisée Ligue Contre le Cancer, Villeneuve d'Ascq, France.",
"Inserm UMR1277, CNRS UMR9020-CANTHER, Université de Lille, Lille University Hospital, Lille, France.",
"Inserm UMR1277, CNRS UMR9020-CANTHER, Université de Lille, Lille University Hospital, Lille, France.",
"Université Lille, Inserm, CHU Lille, U1192, Laboratoire Protéomique, Réponse Inflammatoire Et Spectrométrie de Masse (PRISM), Villeneuve d'Ascq, France.\nEquipe Labellisée Ligue Contre le Cancer, Villeneuve d'Ascq, France.",
"Université Lille, Inserm, CHU Lille, U1192, Laboratoire Protéomique, Réponse Inflammatoire Et Spectrométrie de Masse (PRISM), Villeneuve d'Ascq, France.\nEquipe Labellisée Ligue Contre le Cancer, Villeneuve d'Ascq, France.\nInstitute of Neuroimmunology, Slovak Academy of Sciences, Dúbravská cesta 9, Bratislava, Slovakia.\nCentre for Experimental and Clinical Regenerative Medicine, Clinic of Small Animals, University of Veterinary Medicine and Pharmacy in Kosice, Kosice, Slovakia.",
"Université Lille, Inserm, CHU Lille, U1192, Laboratoire Protéomique, Réponse Inflammatoire Et Spectrométrie de Masse (PRISM), Villeneuve d'Ascq, France. [email protected].\nEquipe Labellisée Ligue Contre le Cancer, Villeneuve d'Ascq, France. [email protected].",
"Université Lille, Inserm, CHU Lille, U1192, Laboratoire Protéomique, Réponse Inflammatoire Et Spectrométrie de Masse (PRISM), Villeneuve d'Ascq, France. [email protected].\nEquipe Labellisée Ligue Contre le Cancer, Villeneuve d'Ascq, France. [email protected]."
] | [
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] | [] | 10.290262 | 5.473006 |
39632397 | 166 | Depletion of Tregs from CD4 | Chimeric antigen receptor T (CAR-T) cell therapy, which targets CD19 for hematological malignancies, represents a breakthrough in cancer immunotherapy. However, some patients may develop resistance to CAR-T treatment, underscoring the importance of optimizing CAR-T design to enhance responsiveness. Here, we investigated the impact of different subpopulations in anti-CD19 CAR-T cells on the tumoricidal effect. Different populations of anti-CD19 CAR-T cells were isolated by magnetic-activated cell sorting (MACS). Their lytic activities on the acute lymphocytic leukemia cell line SUP-B15 and diffuse large B-cell lymphoma EB-3 cell line were examined in a co-culture system. The anti-tumorigenic outcome of different CAR-T cell compositions was evaluated in a xenograft mouse model of EB-3 cells. CD8 | [
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] | 2024-12-05 | 1 | 39632397 | [
"anti-CD19 CAR-T cells",
"different CAR-T cell compositions",
"the acute lymphocytic leukemia cell line",
"large B-cell lymphoma EB-3 cell line",
"different subpopulations",
"magnetic-activated cell sorting",
"Different populations",
"hematological malignancies",
"CAR-T treatment",
"CAR-T design",
"The anti-tumorigenic outcome",
"cancer immunotherapy",
"EB-3 cells",
"a co-culture system",
"CD19",
"CAR-T",
"xenograft",
"resistance",
"a xenograft mouse model",
"responsiveness",
"MACS",
"SUP-B15",
"Their lytic activities",
"the tumoricidal effect",
"a breakthrough",
"the importance",
"CD8",
"the impact",
"some patients",
"EB-3"
] | [
"CAR‐T",
"CD19",
"Tregs",
"cytotoxic",
"tumoricial"
] | 0 | 10.1111/febs.17326 | [
"Sun",
"Liu",
"Zhan",
"Wei",
"XianShi",
"Zhang",
"Duan",
"Zhang",
"Tang",
"Lin",
"Li",
"Lai"
] | [
"Department of Hematology, Yunnan Cancer Hospital, The Third Affiliated Hospital of Kunming Medical University, Peking University Cancer Hospital Yunnan, Kunming, China.",
"Department of Hematology, Yunnan Cancer Hospital, The Third Affiliated Hospital of Kunming Medical University, Peking University Cancer Hospital Yunnan, Kunming, China.",
"Department of Human Anatomy and Histology & Embrology, School of Basic Medical Sciences, Kunming Medical University, China.",
"Department of Hematology, Yunnan Cancer Hospital, The Third Affiliated Hospital of Kunming Medical University, Peking University Cancer Hospital Yunnan, Kunming, China.",
"Department of Hematology, Yunnan Cancer Hospital, The Third Affiliated Hospital of Kunming Medical University, Peking University Cancer Hospital Yunnan, Kunming, China.",
"Department of Hematology, Yunnan Cancer Hospital, The Third Affiliated Hospital of Kunming Medical University, Peking University Cancer Hospital Yunnan, Kunming, China.",
"Department of Hematology, Yunnan Cancer Hospital, The Third Affiliated Hospital of Kunming Medical University, Peking University Cancer Hospital Yunnan, Kunming, China.",
"Department of Hematology, Yunnan Cancer Hospital, The Third Affiliated Hospital of Kunming Medical University, Peking University Cancer Hospital Yunnan, Kunming, China.",
"Department of Hematology, Yunnan Cancer Hospital, The Third Affiliated Hospital of Kunming Medical University, Peking University Cancer Hospital Yunnan, Kunming, China.",
"Yunnan College of Business Management, Kunming, China.",
"Yunnan College of Business Management, Kunming, China.",
"Department of Hematology, Yunnan Cancer Hospital, The Third Affiliated Hospital of Kunming Medical University, Peking University Cancer Hospital Yunnan, Kunming, China."
] | [
"39632397"
] | [] | 7.567563 | 5.102536 |
39631075 | 167 | New Strategies for Enhancing Enrollment of Underrepresented Minorites in Lymphoma Clinical Trials. | New lymphoma treatments, including chimeric antigen receptor (CAR) T-cells, bispecific antibodies, and immune checkpoint inhibitors, have significantly improved patient outcomes. Despite these therapeutic advances, only 2%-3% of adult cancer patients participate in clinical trials. This participation is even lower among certain groups, including ethnic and racial minorities, individuals with low socioeconomic status, rural residents, older adults, and young adults. Under-representation of these groups in clinical trials limits the generalizability of trial results and is detrimental to those populations that do not receive equal access to novel therapies. Although racial and ethnic minorities constitute over 40% of the U.S. population, they make up only about 15% of clinical trial participants. The US FDA now requires sponsors seeking regulatory approval for therapies via registrational clinical trials to submit a plan to ensure diversity among trial participants. This article addresses Strategies for Enhancing Enrollment of Underrepresented Minorities in Lymphoma Clinical Trials. | [
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] | [] | 0 | 10.1182/bloodadvances.2024012981 | [
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] | [
"The University of Texas MD Anderson Cancer Center, Houston, Texas, United States.",
"City of Hope, Duarte, California, United States."
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] | [] | 7.041292 | 4.649333 |
39631041 | 168 | Phase I Trial of MCARH109, a G Protein-Coupled Receptor Class C Group 5 Member D (GPRC5D)-Targeted Chimeric Antigen Receptor T-Cell Therapy for Multiple Myeloma: An Updated Analysis. | MCARH109 is a first-in-class G protein-coupled receptor, class C, group 5, member D (GPRC5D)-targeted chimeric antigen receptor (CAR) T-cell therapy for patients with relapsed/refractory multiple myeloma. This phase I clinical trial included 17 patients and determined that MCARH109 is safe at a maximum tolerated dose of 150 × 10 | [
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] | 2024-12-04 | 1 | 39631041 | [
"class C",
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"group",
"relapsed/refractory multiple myeloma",
"a maximum tolerated dose",
"first",
"CAR) T-cell therapy",
"I clinical trial",
"17 patients",
"150 ×",
"150",
"17",
"5"
] | [] | 0 | 10.1200/JCO-24-01785 | [
"Jurgens",
"Firestone",
"Chaudhari",
"Hosszu",
"Devlin",
"Shah",
"Landa",
"McAvoy",
"Lesokhin",
"Korde",
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"Shah",
"Landau",
"Chung",
"Scordo",
"Eren",
"Dogan",
"Giralt",
"Park",
"Rivière",
"Brentjens",
"Smith",
"Wang",
"Usmani",
"Mailankody"
] | [
"Myeloma Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY.",
"Myeloma Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY.",
"Cell Therapy and Cell Engineering Facility, Memorial Sloan Kettering Cancer Center, New York, NY.",
"Immune Discovery and Modeling Service, Memorial Sloan Kettering Cancer Center, New York, NY.",
"Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, NY.",
"Myeloma Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY.",
"Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, NY.",
"Immune Discovery and Modeling Service, Memorial Sloan Kettering Cancer Center, New York, NY.",
"Myeloma Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY.\nCellular Therapy Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY.",
"Myeloma Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY.",
"Myeloma Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY.",
"Myeloma Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY.",
"Myeloma Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY.",
"Cellular Therapy Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY.\nAdult Bone Marrow Transplant Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY.",
"Cellular Therapy Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY.\nAdult Bone Marrow Transplant Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY.",
"Cellular Therapy Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY.\nAdult Bone Marrow Transplant Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY.",
"Cellular Therapy Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY.\nAdult Bone Marrow Transplant Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY.",
"Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY.",
"Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY.",
"Cellular Therapy Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY.\nAdult Bone Marrow Transplant Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY.",
"Cellular Therapy Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY.\nLeukemia Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY.",
"Cell Therapy and Cell Engineering Facility, Memorial Sloan Kettering Cancer Center, New York, NY.",
"Department of Medicine, Roswell Park Comprehensive Cancer Center, Buffalo, NY.",
"Department of Medical Oncology, Dana-Farber Cancer Center, Boston, MA.",
"Cell Therapy and Cell Engineering Facility, Memorial Sloan Kettering Cancer Center, New York, NY.",
"Myeloma Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY.\nCellular Therapy Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY.\nAdult Bone Marrow Transplant Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY.",
"Myeloma Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY.\nCellular Therapy Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY."
] | [
"39631041"
] | [] | 5.122412 | 5.836634 |
39630061 | 169 | Honing CAR T cells to tackle acute myeloid leukemia. | Acute myeloid leukemia (AML) remains a dismal disease with poor prognosis, particularly in the relapsed/refractory (r/r) setting. Chimeric antigen receptor (CAR) therapy has yielded remarkable clinical results in other leukemias and thus has, in principle, the potential to achieve similar outcomes in r/r AML. Re-directing the approved CD19-specific CAR designs against the myeloid antigens CD33, CD123 or CLEC12A has occasionally yielded morphological leukemia-free states (MLFS) but has so far been marred by threatening myeloablation and early relapses. These safety and efficacy limitations owe in large part to the challenge of identifying suitable target antigens and designing adequate receptors for effective recognition and safe elimination of AML. Building on lessons learned from the initial clinical attempts, a new wave of CAR strategies relying on alternative target antigens and innovative CAR designs is about to enter clinical evaluation. Adapted multi-antigen targeting, logic-gating and emerging cell engineering solutions offer new possibilities to better direct T cell specificity and sensitivity towards AML. Pharmacologic modulation and genetic epitope engineering may extend these approaches by augmenting target expression in AML cells or minimizing target expression in normal hematopoietic cells. On/off switches or CAR T cell depletion may curb excessive or deleterious CAR activity. Investigation of AML-intrinsic resistance and leukemic microenvironmental factors is poised to reveal additional targetable AML vulnerabilities. We summarize here the findings, challenges and new developments of CAR therapy for AML. These illustrate the need to specifically adapt CAR strategies to the complex biology of AML to achieve better therapeutic outcomes. | [
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] | 2024-12-04 | 1 | 39630061 | [
"AML cells",
"CAR T cell depletion",
"CAR strategies",
"innovative CAR designs",
"CAR therapy",
"CAR",
"AML",
"additional targetable AML vulnerabilities",
"suitable target antigens",
"alternative target antigens",
"better direct T cell specificity",
"target expression",
"normal hematopoietic cells",
"Acute myeloid leukemia",
"remarkable clinical results",
"new developments",
"new possibilities",
"other leukemias",
"genetic epitope engineering",
"clinical evaluation",
"better therapeutic outcomes",
"r/r AML",
"leukemic microenvironmental factors",
"adequate receptors",
"similar outcomes",
"excessive or deleterious CAR activity",
"large part",
"AML-intrinsic resistance",
"effective recognition",
"poor prognosis"
] | [] | 0 | 10.1182/blood.2024024063 | [
"Haubner",
"Subklewe",
"Sadelain"
] | [
"Memorial Sloan Kettering Cancer Center, New York, New York, United States.",
"University Hospital, LMU Munich, Munich, Germany.",
"MSKCC, New York, New York, United States."
] | [
"39630061"
] | [] | 6.914766 | 7.155727 |
39629159 | 170 | Analyzing functional heterogeneity of effector cells for enhanced adoptive cell therapy applications. | Cellular effector function assays traditionally rely on bulk cell populations that mask complex heterogeneity and rare subpopulations. The Xdrop® droplet technology facilitates high-throughput compartmentalization of viable single cells or single-cell pairs in double-emulsion droplets, enabling the study of single cells or cell-cell interactions at an individual level. Effector cell molecule secretion and target cell killing can be evaluated independently or in combination. Compatibility with a wide range of commercial assay reagents allows for single-cell level readouts using common laboratory techniques such as flow cytometry or microscopy. Moreover, individual cells of interest can be viably isolated for further investigation or expansion. Here we demonstrate the application of the double-emulsion droplet technology with a range of cell types commonly utilized for adoptive cell therapy of cancer: natural killer cells, blood-derived T cells, tumor-infiltrating lymphocytes, and chimeric antigen receptor T cells. Single-cell compartmentalization offers unparalleled resolution, serving as a valuable tool for advancing the development and understanding of cellular therapy products. | [
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] | [
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"cell characterization",
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] | 0 | 10.1016/j.iotech.2024.100738 | [
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"Hulen",
"Petersen",
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"Department of Oncology, National Center for Cancer Immune Therapy (CCIT-DK), Copenhagen University Hospital, Herlev, Denmark.\nSamplix ApS, Birkerød, Denmark.",
"Department of Oncology, National Center for Cancer Immune Therapy (CCIT-DK), Copenhagen University Hospital, Herlev, Denmark.",
"Samplix ApS, Birkerød, Denmark.",
"Samplix ApS, Birkerød, Denmark.",
"Samplix ApS, Birkerød, Denmark.",
"Department of Oncology, National Center for Cancer Immune Therapy (CCIT-DK), Copenhagen University Hospital, Herlev, Denmark.\nDepartment of Health Technology, Technical University of Denmark, Lyngby, Denmark.",
"Department of Oncology, National Center for Cancer Immune Therapy (CCIT-DK), Copenhagen University Hospital, Herlev, Denmark.",
"Department of Oncology, National Center for Cancer Immune Therapy (CCIT-DK), Copenhagen University Hospital, Herlev, Denmark.",
"Samplix ApS, Birkerød, Denmark."
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39628840 | 171 | Oxidized mRNA Lipid Nanoparticles for | Chimeric antigen receptor (CAR) monocyte and macrophage therapies are promising solid tumor immunotherapies that can overcome the challenges facing conventional CAR T cell therapy. mRNA lipid nanoparticles (mRNA-LNPs) offer a viable platform for | [
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] | 2024-12-04 | 77 | 39628840 | [
"conventional CAR T cell therapy",
"solid tumor immunotherapies",
"mRNA lipid nanoparticles",
"CAR",
"monocyte",
"Chimeric antigen receptor (CAR) monocyte and macrophage therapies",
"mRNA-LNPs",
"a viable platform",
"the challenges",
"that"
] | [] | 0 | 10.1002/adfm.202312038
10.1038/s41417-023-00600-7
10.1136/jitc-2022-SITC2022.0194 | [
"Mukalel",
"Hamilton",
"Billingsley",
"Li",
"Thatte",
"Han",
"Safford",
"Padilla",
"Papp",
"Parhiz",
"Weissman",
"Mitchell"
] | [
"Department of Bioengineering, University of Pennsylvania, Philadelphia, Pennsylvania 19104, United States.",
"Department of Bioengineering, University of Pennsylvania, Philadelphia, Pennsylvania 19104, United States.",
"Department of Bioengineering, University of Pennsylvania, Philadelphia, Pennsylvania 19104, United States.",
"Department of Bioengineering, University of Pennsylvania, Philadelphia, Pennsylvania 19104, United States.",
"Department of Bioengineering, University of Pennsylvania, Philadelphia, Pennsylvania 19104, United States.",
"Department of Bioengineering, University of Pennsylvania, Philadelphia, Pennsylvania 19104, United States.",
"Department of Bioengineering, University of Pennsylvania, Philadelphia, Pennsylvania 19104, United States.",
"Department of Bioengineering, University of Pennsylvania, Philadelphia, Pennsylvania 19104, United States.",
"Department of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA.",
"Department of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA.\nAbramson Cancer Center, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.",
"Department of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA.\nAbramson Cancer Center, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.",
"Department of Bioengineering, University of Pennsylvania, Philadelphia, Pennsylvania 19104, United States.\nAbramson Cancer Center, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.\nInstitute for Immunology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.\nCardiovascular Institute, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.\nInstitute for Regenerative Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.\nPenn Institute for RNA Innovation, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA."
] | [
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] | [] | 9.928276 | 3.407068 |
39627220 | 172 | Impact of T cell characteristics on CAR-T cell therapy in hematological malignancies. | Chimeric antigen receptor (CAR) T-cell therapy has revolutionized the treatment paradigms for hematological malignancies. However, more than half of these patients cannot achieve sustainable tumor control, partially due to the inadequate potency of CAR-T cells in eradicating tumor cells. T cells are crucial components of the anti-tumor immune response, and multiple intrinsic T-cell features significantly influence the outcomes of CAR-T cell therapy. Herein, we review progressing research on T-cell characteristics that impact the effectiveness of CAR-T cells, including T-cell exhaustion, memory subsets, senescence, regulatory T-cells, the CD4 | [
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] | [] | 0 | 10.1038/s41408-024-01193-6 | [
"Tao",
"Chyra",
"Kotulová",
"Celichowski",
"Mihályová",
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"Department of Haematooncology, University Hospital Ostrava, Ostrava, Czech Republic.\nDepartment of Haematooncology, Faculty of Medicine, University of Ostrava, Ostrava, Czech Republic.",
"Department of Haematooncology, University Hospital Ostrava, Ostrava, Czech Republic.\nDepartment of Haematooncology, Faculty of Medicine, University of Ostrava, Ostrava, Czech Republic.",
"Department of Haematooncology, University Hospital Ostrava, Ostrava, Czech Republic.\nDepartment of Haematooncology, Faculty of Medicine, University of Ostrava, Ostrava, Czech Republic.",
"Department of Haematooncology, University Hospital Ostrava, Ostrava, Czech Republic.\nDepartment of Haematooncology, Faculty of Medicine, University of Ostrava, Ostrava, Czech Republic.",
"Department of Haematooncology, University Hospital Ostrava, Ostrava, Czech Republic.\nDepartment of Haematooncology, Faculty of Medicine, University of Ostrava, Ostrava, Czech Republic.",
"Department of Haematooncology, University Hospital Ostrava, Ostrava, Czech Republic.\nDepartment of Haematooncology, Faculty of Medicine, University of Ostrava, Ostrava, Czech Republic.",
"Department of Haematooncology, University Hospital Ostrava, Ostrava, Czech Republic. [email protected].\nDepartment of Haematooncology, Faculty of Medicine, University of Ostrava, Ostrava, Czech Republic. [email protected]."
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39625613 | 173 | Correlative studies reveal factors contributing to successful CAR-T cell therapies in cancer. | Cellular and targeted immunotherapies have revolutionized cancer treatments in the last several decades. Successful cellular therapies require both effective and durable cytotoxic activity from the immune cells as well as an accessible and susceptible response from targeted cancer cells. Correlative studies from clinical trials as well as real-world data from FDA-approved therapies have revealed invaluable insights about immune cell factors and cancer cell factors that impact rates of response and relapse to cellular therapies. This review focuses on the flagship cellular therapy of engineered chimeric antigen receptor T-cells (CAR-T cells). Within the CAR-T cell compartment, we discuss discoveries about T-cell phenotype, transcriptome, epigenetics, cytokine signaling, and metabolism that inform the cell manufacturing process to produce the most effective and durable CAR-T cells. Within the cancer cell compartment, we discuss mechanisms of resistance and relapse caused by mutations, alternative splicing, post-transcriptional modifications, and cellular reprogramming. Continued correlative and mechanistic studies are required to help us further optimize cellular therapies in a variety of malignancies. | [
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] | 2024-12-03 | 8 | 39625613 | [
"cellular therapies",
"cancer cell factors",
"targeted cancer cells",
"Successful cellular therapies",
"immune cell factors",
"cellular reprogramming",
"cancer treatments",
"post-transcriptional modifications",
"Correlative studies",
"engineered chimeric antigen receptor T-cells",
"the cancer cell compartment",
"the flagship cellular therapy",
"CAR-T cells",
"T-cell phenotype",
"alternative splicing",
"the cell manufacturing process",
"clinical trials",
"cytokine signaling",
"the immune cells",
"invaluable insights",
"relapse",
"response",
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"Cellular and targeted immunotherapies",
"the CAR-T cell compartment",
"Continued correlative and mechanistic studies",
"mutations",
"FDA",
"resistance",
"metabolism"
] | [
"CAR-T cell therapies",
"Cancer",
"Correlative studies"
] | 0 | 10.1007/s10555-024-10232-4
10.1053/j.seminhematol.2018.08.008
10.1158/2159-8290.CD-23-0101
10.3389/FIMMU.2021.684642/BIBTEX
10.1182/BLOOD-2009-09-241398
10.1016/J.COPBIO.2018.01.025
10.1038/s41591-019-0564-6
10.1038/s41467-021-21168-6
10.1038/S41571-019-0184-6 | [
"Yao",
"Davis"
] | [
"Department of Pediatrics, Division of Hematology, Oncology, Stem Cell Transplant and Regenerative Medicine, Stanford University, Stanford, CA, USA.",
"Department of Pediatrics, Division of Hematology, Oncology, Stem Cell Transplant and Regenerative Medicine, Stanford University, Stanford, CA, USA. [email protected].\nCenter for Cancer Cell Therapy, Stanford Cancer Institute, Stanford University, Stanford, CA, USA. [email protected]."
] | [
"39625613",
"30926092",
"36961206",
"34177932",
"20190192",
"29462761",
"31501612",
"30837712"
] | [] | 9.78653 | 3.961311 |
39625587 | 174 | CAR T-cell therapy to treat multiple myeloma: current state and future directions. | Chimeric antigen receptor (CAR) T-cell therapy represents a transformative advancement in treating relapsed or refractory multiple myeloma (MM) in both early- and late-line settings. MM, a plasma cell malignancy, traditionally requires ongoing complex drug regimens, posing significant burdens on patients. In contrast, CAR T-cell therapy offers a one-time treatment option without the need for continuous maintenance therapy. CAR T-cell therapy leverages engineered T-cells to target specific antigens on tumor cells, leading to their elimination. Current approved therapies target B-cell maturation antigen (BCMA); new targets are under investigation, such as G-protein-coupled receptor class C group 5 member D (GPRC5D). Despite its efficacy, CAR T-cell therapy is associated with serious toxicities such as cytokine release syndrome (CRS) and immune-effector cell-associated neurotoxicity syndrome (ICANS), necessitating careful management. The review will provide an overview of the design and manufacturing of CAR T-cells and current FDA indications, as well as challenges and future directions of CAR-T therapy for MM treatment. | [
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39624992 | 175 | CD33-CD123 IF-THEN Gating Reduces Toxicity while Enhancing the Specificity and Memory Phenotype of AML-Targeting CAR-T Cells. | Our study demonstrates the use of "IF-THEN" SynNotch-gated CAR-T cells targeting CD33 and CD123 in AML reduces off-tumor toxicity. This strategy enhances T-cell phenotype, improves expansion, preserves HSPCs, and mitigates cytokine release syndrome-addressing critical limitations of existing AML CAR-T therapies. | [
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] | [] | 0 | 10.1158/2643-3230.BCD-23-0258 | [
"Jambon",
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] | [
"Division of Hematology and Oncology, Department of Pediatrics, Children's Hospital Los Angeles, Keck School of Medicine, University of Southern California, Los Angeles, California.",
"Division of Hematology and Oncology, Department of Pediatrics, Children's Hospital Los Angeles, Keck School of Medicine, University of Southern California, Los Angeles, California.",
"Division of Hematology and Oncology, Department of Pediatrics, Children's Hospital Los Angeles, Keck School of Medicine, University of Southern California, Los Angeles, California.",
"Division of Hematology and Oncology, Department of Pediatrics, Children's Hospital Los Angeles, Keck School of Medicine, University of Southern California, Los Angeles, California.",
"Division of Hematology and Oncology, Department of Pediatrics, Children's Hospital Los Angeles, Keck School of Medicine, University of Southern California, Los Angeles, California.",
"Division of Hematology and Oncology, Department of Pediatrics, Children's Hospital Los Angeles, Keck School of Medicine, University of Southern California, Los Angeles, California.",
"Department of Pathology and Laboratory Medicine, Children's Hospital Los Angeles, Keck School of Medicine, University of Southern California, Los Angeles, California.",
"Department of Pathology and Laboratory Medicine, Children's Hospital Los Angeles, Keck School of Medicine, University of Southern California, Los Angeles, California.",
"Department of Biochemistry and Molecular Biology, University of Calgary, Calgary, Canada.",
"Department of Biochemistry and Molecular Biology, University of Calgary, Calgary, Canada.",
"Division of Hematology and Oncology, Department of Pediatrics, Children's Hospital Los Angeles, Keck School of Medicine, University of Southern California, Los Angeles, California.",
"Division of Hematology and Oncology, Department of Pediatrics, Children's Hospital Los Angeles, Keck School of Medicine, University of Southern California, Los Angeles, California.",
"Division of Hematology and Oncology, Primary Children's Hospital, Huntsman Cancer Institute, Spencer Fox Eccles School of Medicine at the University of Utah, Salt Lake City, Utah.",
"Division of Hematology and Oncology, Department of Pediatrics, Children's Hospital Los Angeles, Keck School of Medicine, University of Southern California, Los Angeles, California.",
"Division of Hematology and Oncology, Department of Pediatrics, Children's Hospital Los Angeles, Keck School of Medicine, University of Southern California, Los Angeles, California.",
"Division of Hematology and Oncology, Department of Pediatrics, Children's Hospital Los Angeles, Keck School of Medicine, University of Southern California, Los Angeles, California.",
"Division of Hematology and Oncology, Department of Pediatrics, Children's Hospital Los Angeles, Keck School of Medicine, University of Southern California, Los Angeles, California."
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39624236 | 176 | Combining the induced pluripotent stem cell (iPSC) technology with chimeric antigen receptor (CAR)-based immunotherapy: recent advances, challenges, and future prospects. | After experiencing many ups and downs, chimeric antigen receptor (CAR)-T cell therapy has reached a milestone as an anti-cancer method, as evidenced by the increasing number of clinical trials and approved products. Nonetheless, there is a real need to optimize CAR-T cell therapy and overcome its existing limitations. The importance of cellular starting material for generating CAR-T cells is undeniable, as the current personalized manufacturing approach is the main roadblock to providing a fast, affordable, and standard treatment for patients. Thus, developing an off-the-shelf CAR-T product is a leading focus in adoptive cell therapy. Several biotech companies worldwide are focused on developing an off-the-shelf CAR-T product from allogeneic sources. Induced pluripotent stem cells (iPSCs) have unique characteristics, making them highly attractive among various allogeneic sources. IPSCs can be modified with CAR, undergo other intended gene manipulations, and then be differentiated into functional hematopoietic lineages with anti-cancer activity. Moreover, iPSCs provide an unlimited cell source, simplifying the setting of a standard treatment protocol by generating a homogenous population of resulting cells and reducing batch-to-batch inconsistency. In this review, we delve into the manufacturing of iPSC-derived CAR-T (iCAR-T) cells and discuss the path and challenges of their clinical translation. We also introduce some iPSC-derived cellular alternatives to conventional iCAR-αβ-T cells, including iCAR-T cells with a limited TCR diversity, iCAR-NK, iCAR-macrophages, and iCAR-neutrophils and discuss their relative advantages and disadvantages as well as their differentiation from iPSCs in compliance with cGMP. Finally, we reviewed iPSC-derived CAR-engineered cells being evaluated in clinical trials. | [
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10.1182/blood.2019000621 | [
"Alidadi",
"Barzgar",
"Zaman",
"Paevskaya",
"Metanat",
"Khodabandehloo",
"Moradi"
] | [
"Department of Anatomy, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran.",
"Department of Anatomical Sciences, School of Medicine, Zahedan University of Medical Sciences, Zahedan, Iran.",
"Department of Genetics, Islamic Azad University Tehran Medical Branch, Tehran, Iran.",
"Department of Infectious Diseases, Institute of Public Health named after F.F. Erisman, I.M. Sechenov First Moscow State Medical University of the Ministry of Health of the Russian Federation (Sechenov University), Moscow, Russia.",
"Faculty of Medicine, Zahedan University of Medical Sciences, Zahedan, Sistan and Baluchestan, Iran.",
"Department of Immunology, School of Medicine, Hamadan University of Medical Sciences, Hamadan, Iran.",
"Hematology and blood transfusion science department, School of Allied Medical Sciences, Tehran University of Medical Sciences, Tehran, Iran."
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39624055 | 177 | IL-12 encoding oNDV synergizes with CAR-T cells in orthotopic models of non-small cell lung cancer. | Systemic administration of oncolytic viruses (OVs) is a promising approach for targeting metastatic solid tumors, but their anti-tumor activity is limited by pre-existing neutralizing antibodies against common human viruses. Therefore, investigators have developed OVs derived from non-human host viruses. Successful implementation of this strategy requires that the viral vector selectively infects and replicates within human cancer cells. Newcastle disease virus (NDV) is an avian paramyxovirus that, as NDV-based OVs (oNDVs), has demonstrated safety and activity against multiple human tumors in clinical trials. Their use as a single agent, however, is insufficient to cure tumors. Similarly, chimeric antigen receptor-modified T cells (CAR-T cells) enable systemic targeting of cancer cells but have limited anti-tumor effects against bulky solid tumors, in part due to the immunosuppressive tumor environment. In this study, we evaluated the anti-tumor effects of combining systemic oNDV and CAR-T cell treatments. In models of non-small cell lung carcinoma (NSCLC), we found that oNDV itself and interleukin (IL)-12 derived from oNDVs enhance HER2-directed CAR-T cell anti-tumor activity and persistence | [
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10.12688/f1000research.7563.2 | [
"Rosewell Shaw",
"Morita",
"Porter",
"Tu",
"Biegert",
"Agrawal",
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"Brenner",
"Suzuki"
] | [
"Department of Medicine, Baylor College of Medicine, Houston, TX, USA.\nCenter for Cell and Gene Therapy, Baylor College of Medicine, Texas Children's Hospital, Houston Methodist Hospital, Houston, TX, USA.\nDepartment of Biology, School of Science and Engineering, Benedict College, Columbia, SC, USA.",
"Department of Medicine, Baylor College of Medicine, Houston, TX, USA.\nCenter for Cell and Gene Therapy, Baylor College of Medicine, Texas Children's Hospital, Houston Methodist Hospital, Houston, TX, USA.\nDepartment of Pediatrics, Shinshu University School of Medicine, Matsumoto, Japan.\nInstitute for Biomedical Sciences, Interdisciplinary Cluster for Cutting Edge Research, Shinshu University, Matsumoto, Japan.",
"Department of Medicine, Baylor College of Medicine, Houston, TX, USA.\nCenter for Cell and Gene Therapy, Baylor College of Medicine, Texas Children's Hospital, Houston Methodist Hospital, Houston, TX, USA.",
"AstraZeneca, Gaithersburg, MD, USA.",
"Department of Medicine, Baylor College of Medicine, Houston, TX, USA.\nCenter for Cell and Gene Therapy, Baylor College of Medicine, Texas Children's Hospital, Houston Methodist Hospital, Houston, TX, USA.",
"AstraZeneca, Gaithersburg, MD, USA.",
"AstraZeneca, Gaithersburg, MD, USA.",
"Department of Medicine, Baylor College of Medicine, Houston, TX, USA.\nCenter for Cell and Gene Therapy, Baylor College of Medicine, Texas Children's Hospital, Houston Methodist Hospital, Houston, TX, USA.\nDepartment of Pediatrics, Baylor College of Medicine, Houston, TX, USA.",
"Department of Medicine, Baylor College of Medicine, Houston, TX, USA.\nCenter for Cell and Gene Therapy, Baylor College of Medicine, Texas Children's Hospital, Houston Methodist Hospital, Houston, TX, USA."
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39622760 | 178 | [BCMA chimeric antigen receptor T cells therapy re-treatment of a patient with recurrent/refractory IgD multiple myeloma: A case report and literature review]. | Multiple myeloma (MM) is a malignant plasma cell disease that currently cannot be cured. Several new drugs have continuously been introduced in the recent years. New drugs targeting B-cell maturation antigen (BCMA) have greatly improved the efficacy and prognosis of MM compared with traditional treatments. This article reports the case of an IgD type relapsed and refractory MM patient with poor efficacy of BCMA×CD3 bispecific antibody. The patient achieved deep remission after receiving BCMA-targeted CAR-T cell therapy after initial seven lines of treatment. Literature review was also conducted to improve the clinical physicians' understanding of BCMA target therapy for relapsed and refractory MM patients.
多发性骨髓瘤（MM）是一种恶性浆细胞疾病，目前仍无法治愈。近年来，新药不断问世，与传统治疗相比，以B细胞成熟抗原（BCMA）为靶点的新药极大地改善了MM的疗效及预后。本文报道1例BCMA×CD3双特异性抗体治疗失败的IgD型复发难治MM患者，经过七线治疗，再次接受基于BCMA靶点的CAR-T细胞治疗后获得深度缓解，并进行相关文献复习，以期提高临床医师对复发难治MM患者BCMA靶点再治疗的认识。. | [
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10.1016/j.jtct.2020.12.017 | [
"Gu",
"Qiang",
"Lu",
"Feng",
"Du"
] | [
"Department of Hematology, The Myeloma & Lymphoma Center, The Second Affiliated Hospital of Naval Medical University (Shanghai Changzheng Hospital), Shanghai 200003, China.",
"Department of Hematology, The Myeloma & Lymphoma Center, The Second Affiliated Hospital of Naval Medical University (Shanghai Changzheng Hospital), Shanghai 200003, China.",
"Department of Hematology, The Myeloma & Lymphoma Center, The Second Affiliated Hospital of Naval Medical University (Shanghai Changzheng Hospital), Shanghai 200003, China.",
"Department of Hematology, The Myeloma & Lymphoma Center, The Second Affiliated Hospital of Naval Medical University (Shanghai Changzheng Hospital), Shanghai 200003, China.",
"Department of Hematology, The Myeloma & Lymphoma Center, The Second Affiliated Hospital of Naval Medical University (Shanghai Changzheng Hospital), Shanghai 200003, China."
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39622582 | 179 | Integrating binding affinity and tonic signaling enables a rational CAR design for augmented T cell function. | The success of chimeric antigen receptor (CAR) T cell therapy for hematological malignancies has not yet translated into long-term elimination of solid tumors indicating the need for adequately tuning CAR T cell functionality.
We leveraged a translational pipeline including biophysical characterization and structural prediction of the CAR binding moiety, evaluation of cellular avidity, synapse formation, T cell motility, and functional capacities under repetitive target challenge and in sustained tumor control.
As an example of clinical relevance, we derived a panel of anti-Her2 CARs covering a 4-log affinity range, all expected to target the same Her2 epitope. The same scFv mutations increased both antigen-specific affinity, cellular avidity, and antigen-independent "tonic" signaling; above a minimum threshold, raise in affinity translated into functional avidity in a non-linear fashion. In this case, replacement by amino acids of higher hydrophobicity within the scFv coincidentally augmented affinity, non-specific binding, spontaneous CAR clustering, and tonic signaling, all together relating to T cell functionality in an integrated fashion.
Data emphasize that tonic signaling is not always due to the positive charge but can be driven by hydrophobic interactions of the scFv. CAR binding affinity above the threshold and tonic signaling are required for sustained T cell functionality in antigen rechallenge and long-term tumor control. | [
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"CAR T cell functionality",
"T cell functionality",
"sustained T cell functionality",
"CAR binding affinity",
"T cell therapy",
"T cell motility",
"anti-Her2 CARs",
"functional avidity",
"affinity",
"cellular avidity",
"CAR",
"sustained tumor control",
"non-specific binding, spontaneous CAR clustering",
"tonic",
"solid tumors",
"functional capacities",
"chimeric antigen receptor",
"repetitive target challenge",
"biophysical characterization",
"amino acids",
"higher hydrophobicity",
"structural prediction",
"clinical relevance",
"the CAR binding moiety",
"hematological malignancies",
"long-term tumor control",
"synapse formation",
"antigen rechallenge",
"hydrophobic interactions",
"a non-linear fashion"
] | [
"Chimeric antigen receptor - CAR",
"Immunotherapy",
"T cell"
] | 0 | 10.1136/jitc-2024-010208
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10.1073/pnas.2219086120 | [
"Barden",
"Elsenbroich",
"Haas",
"Ertelt",
"Pervan",
"Velas",
"Gergely",
"Szöőr",
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"Bezler",
"Holzinger",
"Friis",
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] | [
"Division of Genetic Immunotherapy, Leibniz Institute for Immunotherapy, Regensburg, Germany.",
"Division of Genetic Immunotherapy, Leibniz Institute for Immunotherapy, Regensburg, Germany.",
"Institute for Drug Discovery, Leipzig University Faculty of Medicine, Leipzig, Germany.",
"Institute for Drug Discovery, Leipzig University Faculty of Medicine, Leipzig, Germany.\nCenter for Scalable Data Analytics and Artificial Intelligence, ScaDS.AI, Dresden/Leipzig, Germany.",
"Division of Genetic Immunotherapy, Leibniz Institute for Immunotherapy, Regensburg, Germany.",
"Institute of Applied Physics, TU Wien, Vienna, Austria.",
"Department of Biophysics and Cell Biology, University of Debrecen Faculty of Medicine, Debrecen, Hungary.",
"Department of Biophysics and Cell Biology, University of Debrecen Faculty of Medicine, Debrecen, Hungary.",
"Division of Genetic Immunotherapy, Leibniz Institute for Immunotherapy, Regensburg, Germany.",
"Division of Genetic Immunotherapy, Leibniz Institute for Immunotherapy, Regensburg, Germany.",
"Division of Genetic Immunotherapy, Leibniz Institute for Immunotherapy, Regensburg, Germany.",
"Department of Health Technology, Technical University of Denmark, Kgs. Lyngby, Denmark.",
"Biophysics and Cell Biology, University of Debrecen, Debrecen, Hungary.",
"Institute of Applied Physics, TU Wien, Vienna, Austria.",
"Institute for Drug Discovery, Leipzig University Faculty of Medicine, Leipzig, Germany.\nCenter for Scalable Data Analytics and Artificial Intelligence, ScaDS.AI, Dresden/Leipzig, Germany.\nFraunhofer Institute for Cell Therapy and Immunology (IZI), Leipzig, Germany.",
"Department I Internal Medicine, University Hospital Cologne, and Center for Molecular Medicine Cologne, University of Cologne, Cologne, Germany.",
"Division of Genetic Immunotherapy, Leibniz Institute for Immunotherapy, Regensburg, Germany [email protected]."
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] | [] | 8.553521 | 5.047987 |
39622581 | 180 | Impact of immunological aging on T cell-mediated therapies in older adults with multiple myeloma and lymphoma. | The treatment landscape for lymphoma and multiple myeloma, which disproportionally affect older adults, has been transformed by the advent of T cell-mediated immunotherapies, including immune checkpoint inhibition, T cell-engaging bispecific antibodies, and chimeric antigen receptor (CAR) T cell therapy, during the last decade. These treatment modalities re-enable the patient's own immune system to combat malignant cells and offer the potential for sustained remissions and cure for various diseases.Age profoundly affects the physiological function of the immune system. The process of biological aging is largely driven by inflammatory signaling, which is reciprocally fueled by aging-related alterations of physiology and metabolism. In the T cell compartment, aging contributes to T cell senescence and exhaustion, increased abundance of terminally differentiated cells, a corresponding attrition in naïve T cell numbers, and a decrease in the breadth of the receptor repertoire. Furthermore, inflammatory signaling drives aging-related pathologies and contributes to frailty in older individuals. Thus, there is growing evidence of biological aging modulating the efficacy and toxicity of T cell-mediated immunotherapies.Here, we review the available evidence from biological and clinical studies focusing on the relationship between T cell-mediated treatment of hematologic malignancies and age. We discuss biological features potentially impacting clinical outcomes in various scenarios, and potential strategies to improve the safety and efficacy of immune checkpoint inhibitors, T cell-engaging bispecific antibodies, and CAR-T cell therapy in older patients. | [
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] | 2024-12-03 | 176 | 39622581 | [
"naïve T cell numbers",
"T cell therapy",
"T cell senescence",
"malignant cells",
"T cell-mediated treatment",
"biological aging",
"T cell-mediated immunotherapies",
"immune checkpoint inhibition",
"immune checkpoint inhibitors",
"biological features",
"the T cell compartment",
"CAR-T cell therapy",
"older patients",
"older adults",
"clinical outcomes",
"various scenarios",
"chimeric antigen receptor",
"older individuals",
"terminally differentiated cells",
"inflammatory signaling",
"growing evidence",
"various diseases",
"sustained remissions",
"potential strategies",
"multiple myeloma",
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"Department of Hematology and Stem Cell Transplantation, West German Cancer Center and German Cancer Consortium (DKTK partner site Essen), University Duisburg-Essen, University Hospital Essen, Essen, Nordrhein-Westfalen, Germany.",
"Faculty of Medicine and University Hospital of Cologne, Department I of Internal Medicine, Center for Integrated Oncology Aachen Bonn Cologne Düsseldorf (CIO ABCD) and German Hodgkin Study Group (GHSG), University of Cologne, Cologne, Germany.\nMax Planck Institute for Biology of Ageing, Cologne, Nordrhein-Westfalen, Germany.",
"Department of Hematology and Oncology, University Hospital Marien Hospital Herne, Herne, Nordrhein-Westfalen, Germany.\nInstitute for Artificial Intelligence in Medicine, University Duisburg-Essen, University Hospital Essen, Essen, Nordrhein-Westfalen, Germany.",
"Division of Hematology, The Ohio State University Comprehensive Cancer Center Arthur G James Cancer Hospital and Richard J Solove Research Institute, Columbus, Ohio, USA.",
"Cancer Center Baselland, University of Basel Faculty of Medicine, Basel, Liestal, Switzerland.",
"Cancer Center Baselland, University of Basel Faculty of Medicine, Basel, Liestal, Switzerland.",
"Department of Hematology and Stem Cell Transplantation, West German Cancer Center and German Cancer Consortium (DKTK partner site Essen), University Duisburg-Essen, University Hospital Essen, Essen, Nordrhein-Westfalen, Germany.",
"Department of Geriatrics, Ruhr University Bochum, University Hospital Marien Hospital Herne, Herne, Germany.",
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"Department of Hematology, Oncoimmunotherapy Unit, Hospital Clínic de Barcelona, Barcelona, Spain.",
"Department of Medicine, Division of Geriatrics, Research Center on Aging, Université de Sherbrooke, Sherbrooke, Quebec, Canada.",
"Department of Geriatrics, Ruhr University Bochum, University Hospital Marien Hospital Herne, Herne, Germany [email protected]."
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39620223 | 181 | Case report: CD7-targeted autologous CAR-T therapy for the treatment of T-cell acute lymphoblastic leukemia undergoing allogeneic peripheral blood stem cell transplantation in the long-term follow-up. | Chimeric antigen receptor T-cell (CAR-T) therapy has emerged as a promising approach for treating relapsed/refractory (r/r) T-cell acute lymphoblastic leukemia (T-ALL). However, it is mostly used as a bridging therapy for allogeneic hematopoietic stem cell transplantation (allo-HSCT). Furthermore, secondary allo-HSCT is costly and associated with significantly high treatment-related mortality rate than the primary transplants. In this report, we present the case of an adult T-ALL patient who underwent CD7-targeted autologous CAR-T cell therapy that was not bridged with secondary allo-HSCT.
The adult T-ALL patient relapsed for a third time after undergoing allogeneic peripheral blood stem cell transplantation (PBSCI) and achieving the first complete remission (CR1). Therefore, the patient was administered CD7-targeted autologous CAR-T cell therapy that was not bridged with secondary allo-HSCT. Towards this, the endogenous CD7-deleted CAR (CD7-CAR7) T cells were generated using CRISPR/Cas9 gene-editing technology. However, after the first infusion, the CD7 CAR-T cells did not show significant proliferation when analyzed at two weeks and the patient became positive for peripheral measurable residual disease (MRD). Therefore, after a two-week period, an augmented dose of CAR-T cells was administered. MRD was monitored in the peripheral blood and bone marrow samples. The patient achieved complete remission and did not require targeted treatment after the completion of CD7 CAR-T-cell therapy. The current follow-up data has shown that the patient is negative for MRD and has been disease-free for more than 42 months.
The results of this case study provide evidence for the long-term efficacy of CD7-targeted autologous CAR-T-cell therapy without requiring secondary allo-HSCT in patients with r/r T-ALL that have relapsed after previous allogeneic PBSCT. | [
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] | [
"CD7 CAR-T cells",
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] | 0 | 10.3389/fimmu.2024.1469251
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10.1016/j.beha.2018.09.011 | [
"Li",
"Xia",
"Li",
"Wang",
"Sun",
"Wang",
"Zhang"
] | [
"Department of Hematology, Cangzhou People's Hospital, Cangzhou, China.",
"Department of Hematology, Cangzhou People's Hospital, Cangzhou, China.",
"Department of Hematology, Cangzhou People's Hospital, Cangzhou, China.",
"Department of Clinical Lab, Cangzhou People's Hospital, Cangzhou, China.",
"Department of Hematology, Cangzhou People's Hospital, Cangzhou, China.",
"Department of Pathology, Cangzhou People's Hospital, Cangzhou, China.",
"Department of Hematology, Cangzhou People's Hospital, Cangzhou, China.\nDepartment of Hematology, Qilu Hospital Of Shandong University Dezhou Hospital, Dezhou, China."
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39619015 | 182 | Choice of activation protocol impacts the yield and quality of CAR T cell product, particularly with older individuals. | In clinical chimeric antigen receptor (CAR) T cell therapy, one of the strongest correlates of favorable patient responses is lower levels of differentiation in T cells from the peripheral blood mononuclear cell (PBMC) starting material or the CAR T cell product. T cells from older patients are inherently more differentiated, but we hypothesised that specific activation protocols could be used to limit CAR T cell differentiation during manufacturing, particularly in older patients.
We used PBMCs from young (20-30 years old) and older (60+ years old) healthy donors to generate CAR T cells using two activation protocols: soluble anti-(α) CD3 monoclonal antibody (mAb)
Older samples generated fewer, more differentiated CAR T cells than young samples, and the αCD3/CD28 mAb protocol exacerbated this, further reducing yield and quality. CD28 expression by T cells correlated with CAR T cell differentiation, but T cell differentiation in PBMC starting material was a stronger correlate of CAR T cell differentiation.
Choice of activation protocol can substantially impact on the yield and quality of CAR T cells during manufacturing. This is a key consideration for older patients whose samples already generate a poorer yield and lower quality of CAR T cells. | [
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"older patients",
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"lower quality",
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"PBMC",
"older (60+ years old) healthy donors",
"a stronger correlate",
"the strongest correlates"
] | [
"CAR T cell",
"CD28",
"T cell activation",
"ageing"
] | 0 | 10.1002/cti2.70016 | [
"Mehta",
"Trollope",
"Leung",
"Chinni",
"Iasinskaia",
"Harrison",
"Hughes-Parry",
"Jenkins",
"Kershaw",
"Jaworowski",
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] | [
"School of Health and Biomedical Sciences Royal Melbourne Institute of Technology (RMIT) Bundoora VIC Australia.",
"School of Health and Biomedical Sciences Royal Melbourne Institute of Technology (RMIT) Bundoora VIC Australia.",
"School of Health and Biomedical Sciences Royal Melbourne Institute of Technology (RMIT) Bundoora VIC Australia.",
"School of Health and Biomedical Sciences Royal Melbourne Institute of Technology (RMIT) Bundoora VIC Australia.",
"School of Health and Biomedical Sciences Royal Melbourne Institute of Technology (RMIT) Bundoora VIC Australia.",
"Peter MacCallum Cancer Centre Melbourne VIC Australia.\nSir Peter MacCallum Department of Oncology University of Melbourne Melbourne VIC Australia.",
"Immunology Division The Walter and Eliza Hall Institute of Medical Research Parkville VIC Australia.\nDepartment of Medical Biology University of Melbourne Melbourne VIC Australia.",
"Immunology Division The Walter and Eliza Hall Institute of Medical Research Parkville VIC Australia.\nDepartment of Medical Biology University of Melbourne Melbourne VIC Australia.\nDepartment of Biochemistry and Chemistry, Institute of Molecular Science La Trobe University Bundoora VIC Australia.",
"Peter MacCallum Cancer Centre Melbourne VIC Australia.\nSir Peter MacCallum Department of Oncology University of Melbourne Melbourne VIC Australia.",
"School of Health and Biomedical Sciences Royal Melbourne Institute of Technology (RMIT) Bundoora VIC Australia.\nLife Sciences Discipline Burnet Institute Melbourne VIC Australia.\nDepartment of Infectious Diseases The Alfred Hospital and Monash University Melbourne VIC Australia.",
"Peter MacCallum Cancer Centre Melbourne VIC Australia.\nSir Peter MacCallum Department of Oncology University of Melbourne Melbourne VIC Australia.",
"Australian Cancer Research Foundation (ACRF) Translational Laboratory Royal Melbourne Hospital Melbourne VIC Australia.\nDepartment of Medicine University of Melbourne Melbourne VIC Australia.",
"Australian Cancer Research Foundation (ACRF) Translational Laboratory Royal Melbourne Hospital Melbourne VIC Australia.\nDepartment of Medicine University of Melbourne Melbourne VIC Australia.",
"School of Health and Biomedical Sciences Royal Melbourne Institute of Technology (RMIT) Bundoora VIC Australia.\nDepartment of Biochemistry, Biomedicine Discovery Institute Monash University Clayton VIC Australia."
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] | [] | 8.229144 | 4.206634 |
39617795 | 183 | CAR T-cell therapy for B-cell lymphomas: outcomes and resistance mechanisms. | Chimeric antigen receptor (CAR) T cells are an exciting curative intent approach to the treatment of non-Hodgkin lymphomas (NHLs). Several products have received FDA approval for 2nd or 3rd line indications, and studies are underway for their use earlier in the disease course. These CAR T cells are ex vivo manufactured autologous cell products that specifically target tumor antigens to optimize tumor specificity and minimize off-tumor side effects-in NHLs, this is typically achieved by targeting B-cell antigens. Engagement of the CAR and corresponding antigen is designed to result in T-cell activation and subsequent tumor clearance. While curative for many NHL patients, too many patients fail to respond to or relapse following CAR T-cell treatment, and salvage options post CAR T-cell therapy are limited. Treatment failures occur because of myriad resistance mechanisms including CAR T-cell dysfunction, generalized immune dysregulation, and intrinsic tumor resistance. Focusing on patients with NHL, we review the clinical outcomes of CAR T-cell therapy and the major resistance mechanisms that lead to poor outcomes. We also review the many innovative and encouraging strategies that are being developed to improve CAR T-cell therapy for NHL. | [
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] | 2024-12-02 | 15 | 39617795 | [
"autologous cell products",
"CAR",
"tumor antigens",
"CAR T-cell treatment",
"CAR T-cell therapy",
"CAR T-cell dysfunction",
"intrinsic tumor resistance",
"many NHL patients",
"myriad resistance mechanisms",
"tumor specificity",
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"Several products",
"poor outcomes",
"patients",
"ex vivo",
"salvage options",
"NHLs",
"NHL",
"studies",
"2nd or 3rd line indications"
] | [
"Bispecific CAR T cells",
"CD19",
"Chimeric antigen receptor",
"Non-Hodgkin lymphoma",
"T-cell exhaustion"
] | 0 | 10.1007/s10555-024-10228-0
10.3390/jpm13111595
10.1182/blood-2023-189733
10.1016/j.molimm.2020.01.006
10.3109/10428194.2015.1011640
10.1182/blood-2019-126217
10.1007/s12032-022-01913-7
10.1038/leu.2015.247
10.1126/scitranslmed.aad5222
10.1007/s11864-021-00920-6
10.1182/bloodadvances.2023010607
10.1016/j.immuni.2012.01.015
10.1016/j.immuni.2013.07.013
10.1084/jem.20130392
10.1038/sj.onc.1203159
10.1182/bloodadvances.2020003482
10.3389/fimmu.2023.1178403
10.1080/14712598.2022.2086043
10.1146/annurev-med-042921-024719
10.1182/blood-2018-02-791350 | [
"Kearl",
"Furqan",
"Shah"
] | [
"BMT & Cellular Therapy Program, Division of Hematology & Oncology, Medical College of Wisconsin, Milwaukee, WI, USA.\nDepartment of Pediatrics, Medical College of Wisconsin, Milwaukee, WI, USA.",
"BMT & Cellular Therapy Program, Division of Hematology & Oncology, Medical College of Wisconsin, Milwaukee, WI, USA.",
"BMT & Cellular Therapy Program, Division of Hematology & Oncology, Medical College of Wisconsin, Milwaukee, WI, USA. [email protected]."
] | [
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] | [] | 7.047295 | 5.004557 |
39617755 | 184 | Ultrasound Control of Genomic Regulatory Toolboxes for Cancer Immunotherapy. | There remains a critical need for the precise control of CRISPR (clustered regularly interspaced short palindromic repeats)-based technologies. Here, we engineer a set of inducible CRISPR-based tools controllable by focused ultrasound (FUS), which can penetrate deep and induce localized hyperthermia for transgene activation. We demonstrate the capabilities of FUS-inducible CRISPR, CRISPR activation (CRISPRa), and CRISPR epigenetic editor (CRISPRee) in modulating the genome and epigenome. We show that FUS-CRISPR-mediated telomere disruption primes solid tumours for chimeric antigen receptor (CAR)-T cell therapy. We further deliver FUS-CRISPR in vivo using adeno-associated viruses (AAVs), followed by FUS-induced telomere disruption and the expression of a clinically validated antigen in a subpopulation of tumour cells, functioning as "training centers" to activate synthetic Notch (synNotch) CAR-T cells to produce CARs against a universal tumour antigen to exterminate neighboring tumour cells. The FUS-CRISPR(a/ee) toolbox hence allows the noninvasive and spatiotemporal control of genomic/epigenomic reprogramming for cancer treatment. | [
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] | 2024-12-02 | 89 | 39617755 | [
"CRISPR activation",
"CRISPR epigenetic editor",
"CRISPR",
"tumour cells",
"neighboring tumour cells",
"FUS",
"chimeric antigen receptor",
"solid tumours",
"FUS-inducible CRISPR",
"telomere disruption",
"inducible CRISPR-based tools",
"FUS-CRISPR",
"FUS-induced telomere disruption",
"focused ultrasound",
"transgene activation",
"localized hyperthermia",
"a universal tumour antigen",
"cancer treatment",
"regularly interspaced short palindromic repeats)-based technologies",
"CRISPRee",
"(CAR)-T cell therapy",
"vivo",
"AAVs",
"CARs",
"genomic/epigenomic reprogramming",
"CRISPRa",
"CAR)-T",
"synthetic Notch (synNotch) CAR-T cells",
"the precise control",
"adeno-associated viruses"
] | [] | 0 | 10.1038/s41467-024-54477-7 | [
"Wu",
"Huang",
"Liu",
"He",
"Wang",
"Yan",
"Wang",
"Gao",
"Zhou",
"Yoon",
"Sun",
"Situ",
"Ho",
"Zeng",
"Yuan",
"Zhu",
"Zhou",
"Zhao",
"Liu",
"Kwong",
"Chien",
"Liu",
"Wang"
] | [
"Shu Chien - Gene Lay Department of Bioengineering, Institute of Engineering in Medicine, University of California San Diego, La Jolla, CA, USA. [email protected].\nNational Biomedical Imaging Center, College of Future Technology, Peking University, Beijing, China. [email protected].",
"Shu Chien - Gene Lay Department of Bioengineering, Institute of Engineering in Medicine, University of California San Diego, La Jolla, CA, USA.\nAlfred E. Mann Department of Biomedical Engineering, University of Southern California, Los Angeles, CA, USA.",
"State Key Laboratory of Vascular Homeostasis and Remodeling, Institute of Cardiovascular Sciences, School of Basic Medical Sciences, Peking University Health Science Center, Beijing, China.",
"Shu Chien - Gene Lay Department of Bioengineering, Institute of Engineering in Medicine, University of California San Diego, La Jolla, CA, USA.",
"Alfred E. Mann Department of Biomedical Engineering, University of Southern California, Los Angeles, CA, USA.",
"Academy for Advanced Interdisciplinary Studies, Peking University, Beijing, China.",
"National Biomedical Imaging Center, College of Future Technology, Peking University, Beijing, China.",
"Academy for Advanced Interdisciplinary Studies, Peking University, Beijing, China.",
"National Biomedical Imaging Center, College of Future Technology, Peking University, Beijing, China.",
"Shu Chien - Gene Lay Department of Bioengineering, Institute of Engineering in Medicine, University of California San Diego, La Jolla, CA, USA.\nAlfred E. Mann Department of Biomedical Engineering, University of Southern California, Los Angeles, CA, USA.",
"Institute of Cancer Research, Shenzhen Bay Laboratory, Shenzhen, China.",
"Shu Chien - Gene Lay Department of Bioengineering, Institute of Engineering in Medicine, University of California San Diego, La Jolla, CA, USA.",
"Shu Chien - Gene Lay Department of Bioengineering, Institute of Engineering in Medicine, University of California San Diego, La Jolla, CA, USA.",
"Alfred E. Mann Department of Biomedical Engineering, University of Southern California, Los Angeles, CA, USA.",
"Shu Chien - Gene Lay Department of Bioengineering, Institute of Engineering in Medicine, University of California San Diego, La Jolla, CA, USA.\nAlfred E. Mann Department of Biomedical Engineering, University of Southern California, Los Angeles, CA, USA.",
"Shu Chien - Gene Lay Department of Bioengineering, Institute of Engineering in Medicine, University of California San Diego, La Jolla, CA, USA.\nAlfred E. Mann Department of Biomedical Engineering, University of Southern California, Los Angeles, CA, USA.",
"Alfred E. Mann Department of Biomedical Engineering, University of Southern California, Los Angeles, CA, USA.",
"Section of Cell and Developmental Biology, University of California San Diego, La Jolla, CA, USA.",
"Center for Functional MRI, University of California San Diego, La Jolla, CA, USA.",
"The Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology & Emory University, Atlanta, GA, USA.",
"Shu Chien - Gene Lay Department of Bioengineering, Institute of Engineering in Medicine, University of California San Diego, La Jolla, CA, USA.",
"Shu Chien - Gene Lay Department of Bioengineering, Institute of Engineering in Medicine, University of California San Diego, La Jolla, CA, USA. [email protected].\nAlfred E. Mann Department of Biomedical Engineering, University of Southern California, Los Angeles, CA, USA. [email protected].",
"Shu Chien - Gene Lay Department of Bioengineering, Institute of Engineering in Medicine, University of California San Diego, La Jolla, CA, USA. [email protected].\nAlfred E. Mann Department of Biomedical Engineering, University of Southern California, Los Angeles, CA, USA. [email protected]."
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] | [] | 9.504404 | 2.772022 |
39617146 | 185 | Combinational CAR T-cell therapy for solid tumors: Requisites, rationales, and trials. | Chimeric antigen receptor (CAR) T-cell therapy has achieved potent antitumor efficacy in hematological malignancies; however, because of limitations in CAR T-cell recruitment, infiltration, activation, and functional persistence in the tumor, its efficacy in solid tumors has been suboptimal. To overcome these challenges, combinational strategies that include chemotherapy, radiation therapy, or immune checkpoint inhibitor agent therapy with CAR T-cell therapy are being investigated. The established functional characteristics of the abovementioned therapies provide a rationale for the use of a combinational approach with CAR T cells. Chemotherapy reshapes the peritumoral stroma, decreases the immunosuppressive cell population, and promotes a proinflammatory milieu, all of which allow for increased recruitment, infiltration, and accumulation of CAR T cells. Radiation therapy promotes a chemokine gradient, which augments tumor infiltration by CAR T cells and further increases expression of tumor-associated antigens, allowing for increased activation of CAR T cells. Immune checkpoint inhibitor agent therapy inactivates T-cell exhaustion pathways-most notably, the PD1/PDL1 pathway-thereby improving the functional persistence of CAR T cells and promoting endogenous immunity. In this review, we discuss the requisites and rationales for combinational therapy, and we review 25 ongoing phase I and II clinical trials, of which 4 use chemotherapy, 3 use radiation therapy, 11 use immunotherapy, and 7 use another agent. While safety, efficacy, and improved outcomes are the primary goals of these ongoing studies, the knowledge gained from them will help pave the way for subsequent studies focused on optimizing combinational regimens and identifying predictive biomarkers. | [
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] | 2024-12-02 | 1 | 39617146 | [
"CAR T cells",
"combinational therapy",
"Radiation therapy",
"radiation therapy",
"Immune checkpoint inhibitor agent therapy",
"immune checkpoint inhibitor agent therapy",
"CAR T-cell therapy",
"combinational regimens",
"combinational strategies",
"tumor infiltration",
"CAR T-cell recruitment",
"functional persistence",
"potent antitumor efficacy",
"subsequent studies",
"solid tumors",
"T-cell exhaustion pathways",
"CAR) T-cell therapy",
"increased activation",
"efficacy",
"increased recruitment",
"infiltration",
"Chemotherapy",
"chemotherapy",
"Chimeric antigen receptor",
"the immunosuppressive cell population",
"improved outcomes",
"rationales",
"clinical trials",
"hematological malignancies",
"the abovementioned therapies"
] | [
"CAR T cells",
"Checkpoint blockade",
"Chemotherapy",
"Combinational therapy",
"Immunotherapy",
"Radiation therapy",
"Regional delivery"
] | 0 | 10.1016/j.pharmthera.2024.108763 | [
"Misawa",
"Bhat",
"Adusumilli",
"Hou"
] | [
"Thoracic Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, NY 10065, USA.",
"Thoracic Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, NY 10065, USA. Electronic address: [email protected].",
"Thoracic Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, NY 10065, USA; Center for Cell Engineering, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, NY 10065, USA. Electronic address: [email protected].",
"Thoracic Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, NY 10065, USA."
] | [
"39617146"
] | [] | 10.050221 | 4.333467 |
39617098 | 186 | Real-world Outcomes of Commercial Tisagenlecleucel for Children, Adolescents, and Young Adults With Acute Lymphoblastic Leukemia in Japan. | Chimeric antigen receptor (CAR) T cells are a major new treatment option for children, adolescents, and young adults (CAYA) patients with relapsed and refractory (R/R) B cell acute lymphoblastic leukemia (B-ALL). Therefore, accumulating evidence from real-world experiences of CAR-T outcomes in various regions worldwide is important, particularly when comparing outcomes of patients with differing medical and ethnic backgrounds. More than 5 years have passed since tisagenlecleucel was approved in Japan. Here, we report a retrospective, multi-institutional investigation examining the association between baseline parameters and clinical outcomes. The aim was to investigate real-world experience and to better comprehend the efficacy of commercial tisagenlecleucel. A nationwide consortium called the Japan CAR-T Consortium conducted a retrospective, multicenter study of CAYA patients who received CAR-T cell treatment with commercial tisagenlecleucel. Forty-two patients with R/R B-ALL whose leukapheresis samples were shipped to Novartis for commercial tisagenlecleucel manufacture were included in the analysis. All infused patients were included in the response, toxicity, and survival analyses. The best overall response rate was 93%. The 1-year overall survival and event-free survival (EFS) rates after infusion were 82% and 56%, respectively. Twenty-seven (64%) had low disease burden (LB, defined as <5% bone marrow [BM] lymphoblasts) prior to tisagenlecleucel infusion. LB was associated with superior outcomes, with a 1-year EFS rate of 80% compared with 24% in high disease burden (≧5% BM lymphoblasts). Multivariate analysis identified an association between prior hematopoietic stem cell transplantation (HSCT) (n = 23, 55%) and superior outcomes, with a 1-year EFS rate of 75% compared with 24% for patients without prior HSCT. This first analysis of CAYA patients with R/R B-ALL undergoing treatment with commercial tisagenlecleucel in Japan reports an efficacy similar to that in clinical trials and other real-world studies and confirms that LB and prior HSCT are associated with superior EFS. | [
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] | 2024-12-02 | 1 | 39617098 | [
"CAYA patients",
"patients",
"superior outcomes",
"prior hematopoietic stem cell transplantation",
"clinical outcomes",
"commercial tisagenlecleucel manufacture",
"commercial tisagenlecleucel",
"prior HSCT",
"survival analyses",
"outcomes",
"low disease burden",
"high disease burden",
"superior EFS",
"CAR",
"R/R B",
"CAR-T cell treatment",
"Multivariate analysis",
"CAYA",
"treatment",
"Japan",
"clinical trials",
"<5% bone marrow",
"other real-world studies",
"HSCT",
"real-world experience",
"real-world experiences",
"CAR-T outcomes",
"young adults",
"tisagenlecleucel",
"baseline parameters"
] | [
"B cell acute lymphoblastic leukemia",
"CAR-T cell therapy",
"Children, adolescents, and young adults",
"Real-world outcomes"
] | 0 | 10.1016/j.jtct.2024.11.016 | [
"Kato",
"Tomizawa",
"Kato",
"Hirabayashi",
"Manabe",
"Irie",
"Sasahara",
"Arakawa",
"Koh",
"Sakaguchi",
"Sugiyama",
"Ogawa",
"Kamiya",
"Saito",
"Nakazawa",
"Nishio",
"Takahashi",
"Iwai",
"Adachi",
"Takita",
"Miyamura",
"Yokoyama",
"Oba",
"Ueda",
"Koga",
"Hiramatsu"
] | [
"Department of Pediatrics, Graduate School of Medicine, Kyoto University, Kyoto, Japan. Electronic address: [email protected].",
"Children's Cancer Center, National Center for Child Health and Development, Tokyo.",
"Children's Cancer Center, National Center for Child Health and Development, Tokyo; Department of Pediatrics, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.",
"Department of Pediatrics, Hokkaido University Graduate School of Medicine, Sapporo, Japan.",
"Department of Pediatrics, Hokkaido University Graduate School of Medicine, Sapporo, Japan.",
"Department of Pediatrics, Tohoku University Graduate School of Medicine, Sendai, Japan.",
"Department of Pediatrics, Tohoku University Graduate School of Medicine, Sendai, Japan.",
"Department of Hematology/Oncology, Saitama Children's Medical Center, Saitama, Japan.",
"Department of Hematology/Oncology, Saitama Children's Medical Center, Saitama, Japan.",
"Children's Cancer Center, National Center for Child Health and Development, Tokyo.",
"Department of Pediatric Oncology, National Cancer Center Hospital, Tokyo, Japan.",
"Department of Pediatric Oncology, National Cancer Center Hospital, Tokyo, Japan.",
"Department of Pediatrics, Institute of Science Tokyo, Tokyo, Japan.",
"Department of Pediatrics, Shinshu University School of Medicine, Matsumoto, Japan.",
"Department of Pediatrics, Shinshu University School of Medicine, Matsumoto, Japan.",
"Department of Pediatrics, Nagoya University Graduate School of Medicine, Nagoya, Japan.",
"Department of Pediatrics, Nagoya University Graduate School of Medicine, Nagoya, Japan.",
"Department of Pediatrics, Graduate School of Medicine, Kyoto University, Kyoto, Japan.",
"Human Health Sciences, Graduate School of Medicine, Kyoto University, Kyoto, Japan.",
"Department of Pediatrics, Graduate School of Medicine, Kyoto University, Kyoto, Japan.",
"Department of Pediatrics, Osaka University Graduate School of Medicine, Osaka, Japan.",
"Department of Pediatrics, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.",
"Department of Pediatrics, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.",
"Department of Pediatrics, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.",
"Department of Pediatrics, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan; Department of Pediatrics, Kindai University Faculty of Medicine, Osakasayama, Japan.",
"Department of Pediatrics, Graduate School of Medicine, Kyoto University, Kyoto, Japan."
] | [
"39617098"
] | [] | 6.13906 | 5.097103 |
39617017 | 187 | Safety and activity of CTX130, a CD70-targeted allogeneic CRISPR-Cas9-engineered CAR T-cell therapy, in patients with relapsed or refractory T-cell malignancies (COBALT-LYM): a single-arm, open-label, phase 1, dose-escalation study. | Effective treatment options are scarce for relapsed or refractory T-cell lymphoma. This study assesses the safety and activity of CTX130 (volamcabtagene durzigedleucel), a CD70-directed, allogeneic chimeric antigen receptor (CAR) immunotherapy manufactured from healthy donor T cells, in patients with relapsed or refractory T-cell lymphoma.
This single-arm, open-label, phase 1 study was done at ten medical centres across the USA, Australia, and Canada in patients (aged ≥18 years) with relapsed or refractory peripheral T-cell lymphoma or cutaneous T-cell lymphoma, who had received at least one or at least two previous systemic therapy lines, respectively, and had an Eastern Cooperative Oncology Group (ECOG) performance status of 0-1. Patients underwent lymphodepletion with fludarabine 30 mg/m
Between Aug 28, 2020, and May 30, 2023, 41 patients were enrolled and 39 (95%) received CTX130. The median patient follow-up was 7·4 months (IQR 3·1-12·2). 21 (54%) of 39 patients were female and 18 (46%) were male. 24 (62%) patients were White, eight (21%) were Black, three (8%) were Asian, three (8%) were from other racial or ethnic groups, and one (3%) was not reported. The median number of previous lines of anticancer therapy was 2·5 (IQR 1·3-4·0) for patients with peripheral T-cell lymphoma and 5·0 (IQR 5·0-7·0) for patients with cutaneous T-cell lymphoma. Cytokine release syndrome was the most common adverse event, occurring in 26 (67%) of 39 patients (23 were grade 1-2, two were grade 3, and one was a grade 4 dose-limiting toxicity at dose level 4). Grade 1-2 neurotoxic events were observed in four (10%) of 39 patients. The most common grade 3-4 adverse events were neutropenia (14 [36%]), anaemia (11 [28%]), and thrombocytopenia (six [15%]). Serious adverse events occurred in 25 (64%) patients, with CTX130-related serious adverse events in 14 (36%) patients, the most common related serious adverse event being cytokine release syndrome in 11 (28%) patients. 21 patients died, 16 from progressive disease and five from adverse events considered unrelated to CTX130 treatment. 18 of 39 patients (46·2% [95% CI 30·1-62·8) had an objective response. Of those treated at dose level 3 and higher, 16 of 31 patients (51·6% [33·1-69·8]) had objective responses, including six (19·4% [7·5-37·5]) with complete response and ten (32·3% [16·7-51·4]) with a partial response.
In patients with heavily pretreated T-cell lymphoma, CTX130 showed manageable safety and a promising objective response rate. This study shows that allogeneic, readily available CAR T cells can be safely given to patients with relapsed or refractory T-cell lymphoma. A next-generation CAR T-cell therapy containing additional potency gene edits (CTX131) is in clinical development.
CRISPR Therapeutics. | [
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] | 2024-12-02 | 1 | 39617017 | [
"Patients",
"patients",
"Serious adverse events",
"adverse events",
"healthy donor T cells",
"objective responses",
"CTX130 treatment",
"additional potency gene edits",
"Eastern Cooperative Oncology Group",
"anticancer therapy",
"CTX130-related serious adverse events",
"complete response",
"previous lines",
"peripheral T-cell lymphoma",
"cutaneous T-cell lymphoma",
"Cytokine release syndrome",
"cytokine release syndrome",
"CTX130",
"grade",
"relapsed or refractory peripheral T-cell lymphoma",
"readily available CAR T cells",
"CRISPR Therapeutics",
"manageable safety",
"relapsed or refractory T-cell lymphoma",
"21 patients",
"39 patients",
"41 patients",
"10%",
"15%",
"19·4%"
] | [] | 0 | 10.1016/S1470-2045(24)00508-4 | [
"Iyer",
"Sica",
"Ho",
"Prica",
"Zain",
"Foss",
"Hu",
"Beitinjaneh",
"Weng",
"Kim",
"Khodadoust",
"Huen",
"Williams",
"Ma",
"Huang",
"Ganpule",
"Nagar",
"Sripakdeevong",
"Cullingford",
"Karnik",
"Dequeant",
"Patel",
"He",
"Li",
"He",
"Mendonez",
"Keegan",
"Horwitz"
] | [
"Department of Lymphoma and Myeloma, The University of Texas MD Anderson Cancer Center, Houston, TX, USA. Electronic address: [email protected].",
"Department of Oncology, Montefiore Medical Center, Albert Einstein Cancer Center, Bronx, NY, USA.",
"Institute of Haematology, Royal Prince Alfred Hospital and University of Sydney, Camperdown, NSW, Australia.",
"Princess Margaret Cancer Centre, Toronto, Canada.",
"Department of Hematology and Hematopoietic Cell Transplantation, City of Hope, Duarte, CA, USA.",
"Department of Dermatology, Yale School of Medicine, New Haven, CT, USA.",
"Division of Hematology and Hematologic Malignancies, Huntsman Cancer Institute, University of Utah, Salt Lake City, UT, USA.",
"Division of Transplantation and Cellular Therapy, University of Miami Hospital and Clinics, Sylvester Comprehensive Cancer Center, Miami, FL, USA.",
"Division of Blood and Marrow Transplantation and Cellular Therapy, Department of Medicine, Stanford University School of Medicine, Stanford, CA, USA.",
"Department of Dermatology, Stanford University School of Medicine, Stanford, CA, USA.",
"Division of Oncology, Department of Medicine, Stanford University School of Medicine, Stanford, CA, USA.",
"Department of Dermatology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.",
"CRISPR Therapeutics, Boston, MA, USA.",
"CRISPR Therapeutics, Boston, MA, USA.",
"CRISPR Therapeutics, Boston, MA, USA.",
"CRISPR Therapeutics, Boston, MA, USA.",
"CRISPR Therapeutics, Boston, MA, USA.",
"CRISPR Therapeutics, Boston, MA, USA.",
"CRISPR Therapeutics, Boston, MA, USA.",
"CRISPR Therapeutics, Boston, MA, USA.",
"CRISPR Therapeutics, Boston, MA, USA.",
"CRISPR Therapeutics, Boston, MA, USA.",
"CRISPR Therapeutics, Boston, MA, USA.",
"CRISPR Therapeutics, Boston, MA, USA.",
"CRISPR Therapeutics, Boston, MA, USA.",
"CRISPR Therapeutics, Boston, MA, USA.",
"CRISPR Therapeutics, Boston, MA, USA.",
"Memorial Sloan Kettering Cancer Center, New York, NY, USA."
] | [
"39617017"
] | [] | 6.025042 | 5.366511 |
39615863 | 188 | CAR-T cell therapy: Challenge and opportunity for effective treatment of small cell lung cancer. | Small cell lung cancer (SCLC) is a devastating malignancy characterized by rapid metastasis, drug resistance, and frequent recurrence. Owing to the paucity of existing therapeutic options, the prognosis of SCLC remains poor. Recently, the combination of immune checkpoint inhibitors and chemotherapy has resulted in modest improvements in treatment responses. In this review, we characterize the biological signature of SCLC and outline the obstacles to current treatment, including impaired antigen presentation and T cell infiltration. These obstacles may potentially be overcome by chimeric antigen receptor (CAR)-T cell therapy. For the first time, we summarize the available data and discuss the future prospects of CAR-T cell therapy for the treatment of SCLC. Given the high heterogeneity and immunosuppressive tumor microenvironment of SCLC, structural modifications of CAR-T cells and combination therapy may be required to elicit a successful antitumor response. Further research, including clinical trials, is needed to determine the suitability of CAR-T cell therapy as a treatment for SCLC. | [
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] | 2024-12-01 | 1 | 39615863 | [
"T cell infiltration",
"Small cell lung cancer",
"combination therapy",
"treatment responses",
"current treatment",
"CAR-T cell therapy",
"impaired antigen presentation",
"chimeric antigen receptor",
"existing therapeutic options",
"immunosuppressive tumor microenvironment",
"CAR-T cells",
"SCLC",
"immune checkpoint inhibitors",
"rapid metastasis",
"drug resistance",
"(CAR)-T cell therapy",
"clinical trials",
"modest improvements",
"structural modifications",
"frequent recurrence",
"Further research",
"chemotherapy",
"CAR)-T",
"first",
"a successful antitumor response",
"the available data",
"a treatment",
"the treatment",
"a devastating malignancy",
"the future prospects"
] | [
"Chimeric antigen receptor T cell therapy",
"Delta-like ligand 3",
"Immunotherapy",
"Small cell lung cancer"
] | 0 | 10.1016/j.bbcan.2024.189228 | [
"Yin",
"Sun",
"Guo",
"Shuai",
"Zhang"
] | [
"Department of Health Management Center & Institute of Health Management, Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China, Chengdu, China.",
"Department of Health Management Center & Institute of Health Management, Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China, Chengdu, China.",
"Department of Health Management Center & Institute of Health Management, Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China, Chengdu, China.",
"Department of Health Management Center & Institute of Health Management, Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China, Chengdu, China. Electronic address: [email protected].",
"Department of Health Management Center & Institute of Health Management, Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China, Chengdu, China. Electronic address: [email protected]."
] | [
"39615863"
] | [] | 7.352695 | 6.408179 |
39614361 | 189 | BCMA CAR-T therapy combined with pomalidomide is a safe and effective treatment for relapsed/refractory multiple myeloma. | B-cell maturation antigen (BCMA)-targeted chimeric antigen receptor T-cell (CAR T-cell) therapy has exhibited remarkable efficacy in refractory or relapsed multiple myeloma (R/R MM), but recurrence and rapid progression of disease are still observed within a short time after treatment. Long-term pomalidomide therapy, which potentiates T-cell functionality, might enhance the efficacy of BCMA CAR T-cell therapy.
We performed a single-center retrospective clinical study. Patients with relapsed or refractory multiple myeloma who received BCMA CAR T-cell infusion were enrolled in our study, and were followed by long-term pomalidomide treatment (4 mg/day) or not one month after infusion. The response and adverse events were assessed after infusion. The effect of pomalidomide on BCMA CAR T-cells was assessed in vitro.
The objective response rate (ORR) of BCMA-CART was 100%. Three months following CAR T-cell infusion, of the 8 patients receiving pomalidomide, except for 2 patients who stopped maintenance therapy and were lost to follow-up, all patients (6/6) achieved VGPR (very good partial response) or CR (complete response), while only 5 patients (5/8) who did not receive pomalidomide treatment achieved VGPR or better. At a median follow-up of 27 months, for the 8 patients who did not receive pomalidomide administration, the median TTP (time to progression) was 5.85 (1-14) months, while the OS (overall survival) was 10.7 (1.2-16) months. Of the 8 patients who received pomalidomide therapy after CAR T-cell infusion, the median TTP was 13 (7-13) months, while the OS was not reached. Moreover, neither long-term hematological toxicity nor drug-induced liver damage was observed during the follow-up period. Mechanistically, pomalidomide promotes antimyeloma efficacy of BCMA CAR T-cells by inhibiting cell apoptosis and enhancing cytoxicity.
Our results confirmed that BCMA CAR T-cell therapy combined with long-term pomalidomide had a low recurrence rate and manageable therapy-related side effects, providing a promising option for treating R/R MM. | [
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] | 2024-11-30 | 45 | 39614361 | [
"pomalidomide therapy",
"cell apoptosis",
"BCMA CAR T-cell therapy",
"BCMA CAR T-cell infusion",
"BCMA CAR T-cells",
"CAR T-cell infusion",
"BCMA",
"pomalidomide",
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"pomalidomide treatment",
"multiple myeloma",
"months",
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"manageable therapy-related side effects",
"treatment",
"progression",
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"TTP"
] | [
"BCMA CAR T-cell therapy",
"Combination therapy",
"Pomalidomide",
"Relapsed/Refractory multiple myeloma (R/R MM)"
] | 0 | 10.1186/s12967-024-05772-w | [
"Yan",
"Tu",
"Cheng",
"Zhang",
"Wang",
"Deng",
"Yu",
"Wang",
"Liu",
"Chu",
"Kang",
"Liu",
"Li"
] | [
"Department of Hematology, The Third Xiangya Hospital, Central South University, Changsha, 410013, Hunan, China.",
"Department of Hematology, The Third Xiangya Hospital, Central South University, Changsha, 410013, Hunan, China.",
"Department of Hematology, The Third Xiangya Hospital, Central South University, Changsha, 410013, Hunan, China.",
"Department of Hematology, The Third Xiangya Hospital, Central South University, Changsha, 410013, Hunan, China.",
"Department of Hematology, The Third Xiangya Hospital, Central South University, Changsha, 410013, Hunan, China.",
"Department of Hematology, The Third Xiangya Hospital, Central South University, Changsha, 410013, Hunan, China.",
"Department of Hematology, The Third Xiangya Hospital, Central South University, Changsha, 410013, Hunan, China.",
"Department of Hematology, The Third Xiangya Hospital, Central South University, Changsha, 410013, Hunan, China.",
"Department of Hematology, The Third Xiangya Hospital, Central South University, Changsha, 410013, Hunan, China.",
"Department of Pathology, The Third Xiangya Hospital, Central South University, Changsha, 410013, Hunan, China.",
"Shanghai Unicar-Therapy Bio-Medicine Technology Co, Shanghai, 201612, China.",
"Department of Hematology, The Third Xiangya Hospital, Central South University, Changsha, 410013, Hunan, China.",
"Department of Hematology, The Third Xiangya Hospital, Central South University, Changsha, 410013, Hunan, China. [email protected]."
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] | 2024-11-29 | 1 | 39612322 | [
"persistent antigen stimulation"
] | [] | 0 | 10.1126/sciimmunol.adk2954 | [
"Zhu",
"Luo",
"Lou",
"Yihunie",
"Wizzard",
"DeVilbiss",
"Muh",
"Ma",
"Shinde",
"Hoar",
"Hu",
"Zhang",
"Biswal",
"DeBerardinis",
"Wu",
"Yao"
] | [
"Department of Immunology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.\nImmunology PhD Program, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.",
"Department of Immunology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.",
"Department of Immunology & Microbiology, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA.",
"Department of Immunology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.\nCancer Biology PhD Program, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.",
"Department of Immunology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.\nImmunology PhD Program, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.",
"Children's Medical Center Research Institute, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.",
"Children's Medical Center Research Institute, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.",
"Department of Microbiology, Immunology, & Molecular Genetics, Long School of Medicine, University of Texas Health Science Center at San Antonio, San Antonio, TX 78229, USA.",
"Department of Immunology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.",
"Department of Immunology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.",
"Department of Immunology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.",
"Department of Microbiology, Immunology, & Molecular Genetics, Long School of Medicine, University of Texas Health Science Center at San Antonio, San Antonio, TX 78229, USA.\nSouth Texas Veterans Health Care System, San Antonio, TX 78229, USA.",
"Department of Environmental Health and Engineering, Johns Hopkins School of Public Health, Baltimore, MD 21205, USA.\nJohns Hopkins School of Medicine, Baltimore, MD 21205, USA.",
"Children's Medical Center Research Institute, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.\nHoward Hughes Medical Institute, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.\nEugene McDermott Center for Human Growth and Development, University of Texas Southwestern, Dallas, TX 75225, USA.",
"Department of Immunology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.\nCellular Networks in Cancer Program, Simmons Comprehensive Cancer Center, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.",
"Department of Immunology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.\nKidney Cancer Program, Simmons Comprehensive Cancer Center, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA."
] | [
"39612322"
] | [] | 33.673309 | 6.90401 |
39612280 | 191 | Commentary: Ovarian Cancer: Path to Effective Treatments. | Despite advancements in cancer therapeutics such as checkpoint inhibitors and some targeted therapies, we have not achieved success in effectively treating ovarian cancer, since these therapeutics only benefit a subset of patients, and also provide short-term protection. The use of chemotherapy and radiation therapy can cause depletion and/or lack of immune cells' function. Chimeric antigen receptor T (CAR-T) cell therapy is found to be effective against several blood-based cancers, but limited success was seen against solid tumors. Targeting fewer antigens and significant side effects of therapy decreases the efficacy of CAR-T cells as immunotherapeutic in solid tumors, even though there is a great drive and significant effort to establish these therapies around the world. Bispecific and tri-specific antibodies have recently been advocated as effective cancer therapeutics. However, at present, these also suffer the fate of CAR-Ts since the loss of antigen on tumor cells will render these therapeutics ineffective. At present, we should design therapeutics that may have synergistic effects on killing/treating tumors. The only way we can establish that will be by learning the mechanisms of actions of immune therapeutics. Thus, advancement in the knowledge and effective strategies are required to develop cancer immuno-therapeutics. We have dedicated our efforts to understand the immunobiology of natural killer (NK) cells. One of our most important discoveries was demonstration of targeting of cancer stem-like cells (CSCs)/poorly differentiated tumors exhibiting lower major histocompability complex class I expression by the NK cells. In addition, we showed that supercharged NK (sNK) cells had great ability to target both CSCs/poorly differentiated and well differentiated ovarian tumors, whereas activated primary NK cells only targeted CSCs/poorly differentiated tumors. Therefore, the use of sNK cells in immunotherapy should result in effective elimination of heterogeneous populations of ovarian tumors. | [
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] | 2024-11-29 | 1 | 39612280 | [
"tumor cells",
"cell therapy",
"effective cancer therapeutics",
"cancer therapeutics",
"activated primary NK cells",
"sNK cells",
"CSCs)/poorly differentiated tumors",
"ovarian tumors",
"ovarian cancer",
"solid tumors",
"immune therapeutics",
"radiation therapy",
"therapeutics",
"therapy",
"effective elimination",
"cancer stem-like cells",
"significant side effects",
"tri-specific antibodies",
"Chimeric antigen receptor",
"CAR-T cells",
"cancer immuno-therapeutics",
"fewer antigens",
"synergistic effects",
"NK",
"immune cells function",
"great ability",
"the NK cells",
"limited success",
"ovarian",
"antigen"
] | [] | 0 | 10.1615/CritRevImmunol.2024053766 | [
"Jewett",
"Memarzadeh",
"Kaur"
] | [
"Division of Oral Biology and Medicine, The Jane and Jerry Weintraub Center for Reconstructive Biotechnology, University of California School of Dentistry, 10833 Le Conte Ave, 90095 Los Angeles, CA, USA; The Jonsson Comprehensive Cancer Center, UCLA School of Dentistry and Medicine, Los Angeles, CA, USA.",
"The Jonsson Comprehensive Cancer Center, University of California, Los Angeles, Los Angeles, CA 90095, USA; Department of Obstetrics and Gynecology, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA, 90095, USA; UCLA Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research, University of California, Los Angeles, Los Angeles, CA 90095, USA; Molecular Biology Institute, University of California, Los Angeles, Los Angeles, CA 90095, USA; The VA Greater Los Angeles Healthcare System, Los Angeles, CA 90073, USA.",
"Division of Oral Biology and Medicine, The Jane and Jerry Weintraub Center for Reconstructive Biotechnology, University of California School of Dentistry, 10833 Le Conte Ave, 90095 Los Angeles, CA, USA."
] | [
"39612280"
] | [] | 11.112698 | 5.128764 |
39611241 | 192 | Blinatumomab for the treatment of acute lymphoblastic leukemia in a real-world setting: clinical vignettes. | Blinatumomab, a CD19/CD3 bispecific T-cell engager; inotuzumab ozogamicin (INO), a CD22 antibody drug conjugate; and chimeric-antigen receptor (CAR) T-cell constructs are novel immune-therapeutic options for treatment of acute lymphoblastic leukemia (ALL). The use of blinatumomab has recently expanded to multiple B-ALL treatment settings. Despite the efficacy of blinatumomab, its use can be challenging in the real-world because of limited experience with its administration and management of toxicities. Optimal use and sequencing of blinatumomab is critical to improve outcomes, reduce undesired toxicities, and decrease discontinuation rates related to such toxicities. Herein, we discuss strategies to address the unique adverse effects of blinatumomab and ways to optimize its administration and integration into the treatment backbone of B-ALL. We outline our approach to combining and sequencing blinatumomab with other immunotherapies, such as INO and CD19 CAR T-cells, and provide recommendations for the management of toxicities and dose-optimization of blinatumomab therapy in clinical practice. | [
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] | 2024-11-29 | 1 | 39611241 | [
"blinatumomab therapy",
"blinatumomab",
"such toxicities",
"undesired toxicities",
"treatment",
"toxicities",
"Optimal use",
"acute lymphoblastic leukemia",
"limited experience",
"INO",
"other immunotherapies",
"inotuzumab ozogamicin",
"discontinuation rates",
"management",
"CD19",
"CAR T-cells",
"clinical practice",
"ALL",
"novel immune-therapeutic options",
"integration",
"CAR) T-cell constructs",
"a CD22 antibody drug conjugate",
"ways",
"outcomes",
"recommendations",
"a CD19/CD3 bispecific T-cell engager",
"the unique adverse effects",
"the treatment backbone",
"strategies",
"multiple B-ALL treatment settings"
] | [
"Blinatumomab",
"cytokine release syndrome",
"neurologic toxicities"
] | 0 | 10.1080/10428194.2024.2426052 | [
"Paul",
"Jabbour",
"Nichols",
"Short",
"Kantarjian"
] | [
"Division of Pharmacy, M.D. Anderson Cancer Center, The University of Texas, Houston, TX, USA.",
"Department of Leukemia, M.D. Anderson Cancer Center, The University of Texas, Houston, TX, USA.",
"Division of Pharmacy, M.D. Anderson Cancer Center, The University of Texas, Houston, TX, USA.",
"Department of Leukemia, M.D. Anderson Cancer Center, The University of Texas, Houston, TX, USA.",
"Department of Leukemia, M.D. Anderson Cancer Center, The University of Texas, Houston, TX, USA."
] | [
"39611241"
] | [] | 6.415715 | 6.482517 |
39609705 | 193 | CAR-armored-cell therapy in solid tumor treatment. | Over the past decade, chimeric antigen receptor (CAR)-T cell therapy has emerged as a revolutionary immunotherapeutic approach to combat cancer. This therapy constructs a CAR on the surface of T cells through genetic engineering techniques. The CAR is formed from a combination of antibody-derived or ligand-derived domains and T-cell receptor (TCR) domains. This enables T cells to specifically bind to and activate against tumor cells. However, the efficacy of CAR-T cells in solid tumors remains inconclusive due to several challenges such as poor tumor trafficking, infiltration, and the immunosuppressive tumor microenvironment (TME). In response, CAR natural killer (CAR-NK) and CAR macrophages (CAR-M) have been developed as complementary strategies for solid tumors. CAR-NK cells do not require HLA compatibility, demonstrate reduced toxicity, and are thus seen as potential substitutes for CAR-T cells. Furthermore, CAR-M immunotherapy is also being researched and has shown phagocytic capabilities and tumor-antigen presentation. This study discusses the features, advantages, and limitations of CAR-T, CAR-NK, and CAR-M cells in the treatment of solid tumors and suggests prospective solutions for enhancing the efficacy of CAR host-cell-based immunotherapy. | [
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] | 2024-11-29 | 163 | 39609705 | [
"tumor cells",
"T cells",
"CAR)-T cell therapy",
"solid tumors",
"poor tumor trafficking",
"CAR macrophages",
"CAR natural killer",
"CAR",
"CAR-T cells",
"CAR-NK cells",
"chimeric antigen receptor",
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"reduced toxicity",
"several challenges",
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"genetic engineering techniques",
"the immunosuppressive tumor microenvironment",
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"combat cancer",
"T-cell receptor (TCR) domains",
"CAR-NK",
"CAR-T, CAR-NK, and CAR-M cells",
"advantages",
"limitations"
] | [
"CAR-M",
"CAR-NK",
"CAR-T",
"Solid tumor"
] | 0 | 10.1186/s12967-024-05903-3 | [
"Liu",
"Xiao",
"Yang",
"Chen",
"Liu",
"Wang",
"Guo",
"Luo"
] | [
"Navy Medical University, Shanghai, 200433, China.",
"Navy Medical University, Shanghai, 200433, China.",
"Navy Medical University, Shanghai, 200433, China.",
"Linyi People's Hospital, Linyi, Shandong, 276000, China.",
"Navy Medical University, Shanghai, 200433, China.",
"Navy Medical University, Shanghai, 200433, China.\nNational Key Laboratory of Medical Immunology & Institute of Immunology, Naval Medical University, Shanghai, China.",
"Navy Medical University, Shanghai, 200433, China. [email protected].\nNational Key Laboratory of Medical Immunology & Institute of Immunology, Naval Medical University, Shanghai, China. [email protected].",
"Navy Medical University, Shanghai, 200433, China. [email protected].\nNational Key Laboratory of Medical Immunology & Institute of Immunology, Naval Medical University, Shanghai, China. [email protected]."
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] | [] | 9.41882 | 4.995112 |
39609126 | 194 | Phase separation of chimeric antigen receptor promotes immunological synapse maturation and persistent cytotoxicity. | Major challenges of chimeric antigen receptor (CAR)-T cell therapy include poor antigen sensitivity and cell persistence. Here, we report a solution to these issues by exploiting CAR phase separation. We found that incorporation of an engineered T cell receptor CD3ε motif, E | [
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] | 2024-11-29 | 1 | 39609126 | [
"chimeric antigen receptor",
"CAR)-T cell therapy",
"CAR phase separation",
"poor antigen sensitivity and cell persistence",
"Major challenges",
"an engineered T cell receptor CD3ε motif",
"CAR)-T",
"E",
"these issues",
"a solution",
"that incorporation",
"We",
"we"
] | [
"CAR-T cell therapy",
"CD2 costimulation",
"antigen sensitivity",
"chimeric antigen receptor",
"exhaustion",
"immunological synapse",
"persistence",
"phase separation",
"tonic signaling",
"trogocytosis"
] | 0 | 10.1016/j.immuni.2024.11.005 | [
"Xu",
"Chen",
"Ren",
"Xu",
"Wu",
"Yang",
"Wang",
"Zhang",
"Zhou",
"Li",
"Zhang",
"Wang",
"Xu"
] | [
"Key Laboratory of Multi-cell Systems, CAS Center for Excellence in Molecular Cell Science, Shanghai Institute of Biochemistry and Cell Biology, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, China.",
"School of Life Science and Technology, ShanghaiTech University, Shanghai, China.",
"Key Laboratory of Multi-cell Systems, CAS Center for Excellence in Molecular Cell Science, Shanghai Institute of Biochemistry and Cell Biology, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, China.",
"Key Laboratory of Systems Health Science of Zhejiang Province, School of Life Science, Hangzhou Institute for Advanced Study, University of Chinese Academy of Sciences, Hangzhou, China.",
"Cancer Center, The First Hospital of Jilin University, Changchun, China.",
"Key Laboratory of Multi-cell Systems, CAS Center for Excellence in Molecular Cell Science, Shanghai Institute of Biochemistry and Cell Biology, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, China.",
"School of Life Science and Technology, ShanghaiTech University, Shanghai, China.",
"School of Life Science and Technology, ShanghaiTech University, Shanghai, China.",
"Key Laboratory of Systems Health Science of Zhejiang Province, School of Life Science, Hangzhou Institute for Advanced Study, University of Chinese Academy of Sciences, Hangzhou, China.",
"Key Laboratory of Multi-cell Systems, CAS Center for Excellence in Molecular Cell Science, Shanghai Institute of Biochemistry and Cell Biology, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, China.",
"Key Laboratory of Multi-cell Systems, CAS Center for Excellence in Molecular Cell Science, Shanghai Institute of Biochemistry and Cell Biology, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, China.",
"School of Life Science and Technology, ShanghaiTech University, Shanghai, China. Electronic address: [email protected].",
"Key Laboratory of Multi-cell Systems, CAS Center for Excellence in Molecular Cell Science, Shanghai Institute of Biochemistry and Cell Biology, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, China; School of Life Science and Technology, ShanghaiTech University, Shanghai, China; Key Laboratory of Systems Health Science of Zhejiang Province, School of Life Science, Hangzhou Institute for Advanced Study, University of Chinese Academy of Sciences, Hangzhou, China. Electronic address: [email protected]."
] | [
"39609126"
] | [] | 8.493553 | 4.709618 |
39608172 | 195 | The role of CD95 in modulating CAR T-cell therapy: Challenges and therapeutic opportunities in oncology. | CAR T cell therapy has revolutionized how we deliver cancer treatment, most notably for hematologic cancers, by compelling T cells to recognize and kill tumor cells. Nevertheless, current obstacles to utilizing this therapy in solid tumors and overcoming cancer resistance include radicalization. This review discusses how CD95 modulation can boost CAR T cell efficacy. Traditionally, CD95 was known to execute apoptosis induction, but it plays a dual role in induced cell death or in supporting cancer cell survival. Recent data have demonstrated that cancer cells escape CD95-mediated apoptosis via the downregulation of CD95, caspase 8 mutation, or the expression of the inhibition protein cFLIP. Additionally, the immunosuppressive tumor microenvironment, containing CD95L expressing immune cells, explains CAR T cell therapy resistance. Furthermore, we characterize the therapeutic potential of CD95 targeted approaches, including CD95L inhibition (APG101) and alterations in CAR T cell manufacturing (tyrosine kinase inhibitors to mitigate fratricide). In this review, we highlight the importance of multi-path way strategies combining CD95 modulation with CAR T cell engineering to overcome resistance, specifically to target tumor cells better and sustain CAR T cell persistence to enhance treatment efficacy in solid tumors. | [
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] | 2024-11-29 | 1 | 39608172 | [
"CAR T cell therapy resistance",
"CAR T cell efficacy",
"CAR T cell manufacturing",
"CAR T cell engineering",
"CAR T cell therapy",
"compelling T cells",
"cancer cells",
"CAR T cell persistence",
"tumor cells",
"cancer cell survival",
"immune cells",
"induced cell death",
"CD95 modulation",
"cancer treatment",
"cancer resistance",
"CD95",
"solid tumors",
"hematologic cancers",
"CD95L inhibition",
"multi-path way strategies",
"apoptosis induction",
"treatment efficacy",
"CD95L",
"resistance",
"Recent data",
"current obstacles",
"tyrosine",
"the immunosuppressive tumor microenvironment",
"inhibitors",
"CD95-mediated apoptosis"
] | [
"Apoptosis",
"CAR T-cell therapy",
"CD95",
"CD95L inhibitors",
"Cancer resistance",
"Immuno-oncology"
] | 0 | 10.1016/j.intimp.2024.113675 | [
"Bhat",
"Altamimi",
"Goyal",
"Goyal",
"Kaur",
"Kumar",
"Sharma",
"Kumar",
"Ali",
"Thapa",
"Negi",
"Singh",
"Gupta"
] | [
"Uttaranchal Institute of Pharmaceutical Sciences, Uttaranchal University, Dehradun, India.",
"Department of Pharmaceutical Chemistry, College of Pharmacy, Prince Sattam Bin Abdulaziz University, Al Kharj 11942, Saudi Arabia.",
"Institute of Pharmaceutical Research, GLA University, Mathura, Uttar Pradesh, India.",
"Department of Biotechnology, Graphic Era (Deemed to be University), Clement Town, Dehradun 248002, India.",
"Department of Allied Healthcare and Sciences, Vivekananda Global University, Jaipur, Rajasthan 303012, India.",
"NIMS Institute of Pharmacy, NIMS University Rajasthan, Jaipur, India.",
"Chandigarh Pharmacy College, Chandigarh Group of College, Jhanjeri, Mohali 140307, Punjab, India.",
"Department of Chemistry, Raghu Engineering College, Visakhapatnam, Andhra Pradesh 531162, India.",
"Centre for Global Health Research, Saveetha Medical College, Saveetha Institute of Medical and Technical Sciences, Saveetha University, India.",
"Uttaranchal Institute of Pharmaceutical Sciences, Uttaranchal University, Dehradun, India.",
"School of Pharmaceutical Sciences, Shoolini University of Biotechnology and Management Sciences, Solan, HP 173212, India.",
"School of Pharmaceutical Sciences, Lovely Professional University, Phagwara, Punjab 144411, India; Faculty of Health, Australian Research Centre in Complementary and Integrative Medicine, University of Technology Sydney, Ultimo, Australia; School of Medical and Life Sciences, Sunway University, 47500, Sunway City, Malaysia.",
"Centre for Research Impact & Outcome, Chitkara College of Pharmacy, Chitkara University, Rajpura, Punjab 140401, India; Centre of Medical and Bio-Allied Health Sciences Research, Ajman University, Ajman, United Arab Emirates. Electronic address: [email protected]."
] | [
"39608172"
] | [] | 9.36023 | 4.615634 |
39607022 | 196 | Bioorthogonal oncolytic-virus nanovesicles combined bio-immunotherapy with CAR-T cells for solid tumors. | Various oncolytic viruses (OVs) have been adopted as therapeutic tools to increase the efficacy of chimeric antigen receptor (CAR)-T cells against solid tumors. However, the therapeutic effect of OVs has been limited by pre-existing neutralizing antibodies and poor targeting delivery for systemic administration. Herein, we propose using bioorthogonal OV nanovesicles to boost the antitumor effects of CAR-T cells in solid tumors by reshaping the tumor microenvironment. Using a cell-membrane nanomimetic technique, we embedded artificial chemical ligands on cancer cell surfaces and then encapsulated lysoviral particles to obtain dual-targeted OV nanovesicles with bioorthogonal targeting and homologous recognition. OVs can be directly encapsulated into cancer cell nanovesicles and exhibit a liposome-like nanostructure, efficient loading, and excellent tumor-targeting capability. Encouragingly, OV nanovesicles efficiently induced tumor-cell apoptosis while sparing normal tissues and cells, thereby inhibiting tumor growth. Administration of viral nanovesicles effectively increased the secretion of anti-tumor cytokines such as IL-2, TNF-α and IFN-γ, and significantly promoted the infiltration and activation of CD8 | [
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] | 2024-11-28 | 1 | 39607022 | [
"cancer cell nanovesicles",
"bioorthogonal OV nanovesicles",
"cancer cell surfaces",
"OV nanovesicles",
"cells",
"solid tumors",
"viral nanovesicles",
"tumor growth",
"pre-existing neutralizing antibodies",
"poor targeting delivery",
"anti-tumor cytokines",
"tumor-cell apoptosis",
"artificial chemical ligands",
"chimeric antigen receptor",
"bioorthogonal targeting",
"therapeutic tools",
"excellent tumor-targeting capability",
"Various oncolytic viruses",
"efficient loading",
"lysoviral particles",
"CAR-T cells",
"OVs",
"normal tissues",
"systemic administration",
"homologous recognition",
"IFN",
"α",
"dual-targeted OV nanovesicles",
"TNF",
"a cell-membrane nanomimetic technique"
] | [] | 0 | 10.1039/d4bm01305k | [
"Huang",
"He",
"Chen",
"Yin",
"Ma",
"Zhu",
"Chen",
"Liang",
"Zhang",
"Pan",
"Cai"
] | [
"Guangdong Key Laboratory of Nanomedicine, CAS-HK Joint Lab of Biomaterials, Shenzhen Institute of Advanced Technology (SIAT), Chinese Academy of Sciences (CAS), Shenzhen, 518055, China. [email protected].",
"Guangdong Key Laboratory of Nanomedicine, CAS-HK Joint Lab of Biomaterials, Shenzhen Institute of Advanced Technology (SIAT), Chinese Academy of Sciences (CAS), Shenzhen, 518055, China. [email protected].\nUniversity of Chinese Academy of Sciences, Beijing, 100049, China.",
"Guangdong Key Laboratory of Nanomedicine, CAS-HK Joint Lab of Biomaterials, Shenzhen Institute of Advanced Technology (SIAT), Chinese Academy of Sciences (CAS), Shenzhen, 518055, China. [email protected].",
"Guangdong Key Laboratory of Nanomedicine, CAS-HK Joint Lab of Biomaterials, Shenzhen Institute of Advanced Technology (SIAT), Chinese Academy of Sciences (CAS), Shenzhen, 518055, China. [email protected].",
"Guangdong Key Laboratory of Nanomedicine, CAS-HK Joint Lab of Biomaterials, Shenzhen Institute of Advanced Technology (SIAT), Chinese Academy of Sciences (CAS), Shenzhen, 518055, China. [email protected].",
"Guangdong Key Laboratory of Nanomedicine, CAS-HK Joint Lab of Biomaterials, Shenzhen Institute of Advanced Technology (SIAT), Chinese Academy of Sciences (CAS), Shenzhen, 518055, China. [email protected].",
"Guangdong Key Laboratory of Nanomedicine, CAS-HK Joint Lab of Biomaterials, Shenzhen Institute of Advanced Technology (SIAT), Chinese Academy of Sciences (CAS), Shenzhen, 518055, China. [email protected].\nUniversity of Chinese Academy of Sciences, Beijing, 100049, China.",
"Guangdong Key Laboratory of Nanomedicine, CAS-HK Joint Lab of Biomaterials, Shenzhen Institute of Advanced Technology (SIAT), Chinese Academy of Sciences (CAS), Shenzhen, 518055, China. [email protected].\nUniversity of Chinese Academy of Sciences, Beijing, 100049, China.",
"Guangdong Key Laboratory of Nanomedicine, CAS-HK Joint Lab of Biomaterials, Shenzhen Institute of Advanced Technology (SIAT), Chinese Academy of Sciences (CAS), Shenzhen, 518055, China. [email protected].\nUniversity of Chinese Academy of Sciences, Beijing, 100049, China.",
"Guangdong Key Laboratory of Nanomedicine, CAS-HK Joint Lab of Biomaterials, Shenzhen Institute of Advanced Technology (SIAT), Chinese Academy of Sciences (CAS), Shenzhen, 518055, China. [email protected].\nUniversity of Chinese Academy of Sciences, Beijing, 100049, China.",
"Guangdong Key Laboratory of Nanomedicine, CAS-HK Joint Lab of Biomaterials, Shenzhen Institute of Advanced Technology (SIAT), Chinese Academy of Sciences (CAS), Shenzhen, 518055, China. [email protected].\nUniversity of Chinese Academy of Sciences, Beijing, 100049, China.\nSino-European Center of Biomedicine and Health, Luohu, Shenzhen 518024, China."
] | [
"39607022"
] | [] | 10.137617 | 3.93114 |
39606234 | 197 | Logic-gated and contextual control of immunotherapy for solid tumors: contrasting multi-specific T cell engagers and CAR-T cell therapies. | CAR-T cell and T cell engager therapies have demonstrated transformational efficacy against hematological malignancies, but achieving efficacy in solid tumors has been more challenging, in large part because of on-target/off-tumor toxicities and sub-optimal T cell anti-tumor cytotoxic functions. Here, we discuss engineering solutions that exploit biological properties of solid tumors to overcome these challenges. Using logic gates as a framework, we categorize the numerous approaches that leverage two inputs instead of one to achieve better cancer selectivity or efficacy in solid tumors with dual-input CAR-Ts or multi-specific TCEs. In addition to the "OR gate" and "AND gate" approaches that leverage dual tumor antigen targeting, we also review "contextual AND gate" technologies whereby continuous cancer-selective inputs such a pH, hypoxia, target density, tumor proteases, and immune-suppressive cytokine gradients can be creatively incorporated in therapy designs. We also introduce the notion of "output directionality" to distinguish dual-input strategies that mechanistically impact cancer cell killing or T cell fitness. Finally, we contrast the feasibility and potential benefits of the various approaches using CAR-T and TCE therapeutics and discuss why the promising "IF/THEN" and "NOT" gate types pertain more specifically to CAR-T therapies, but can also succeed by integrating both technologies. | [
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"Nolan-Stevaux",
"Smith"
] | [
"Oncology Research, Gilead Sciences, Foster City, CA, United States.",
"Cell Biology Research, Kite Pharma, Foster City, CA, United States."
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39606226 | 198 | Preclinical delayed toxicity studies of BCMA CAR T-cell injection in B-NDG mice with multiple myeloma. | Based on the efficacy data from the previous study of B-cell maturation antigen (BCMA) chimeric antigen receptor (CAR) T-cell injection, we further examined the delayed toxicity for 8 weeks after a single dose of BCMA CAR T-cell injection to observe possible toxic reactions.
B-NDG mice transplanted with multiple myeloma (MM) cells were given a single dose of BCMA CAR T-cell injection at two dosages or human normal T cells and then subjected to examinations including clinical signs, weight and food intake measurements, haematology, blood biochemical analysis, cytokine assay, T-lymphocyte subpopulation quantification and histopathology on days 28 and 56 after dosing. In addition, quantitative polymerase chain reaction (qPCR) was used to quantify DNA fragments in different tissues to assess the tissue distribution of CAR and provide a basis for its preclinical safety evaluation and clinical dosing.
In the delayed toxicity study, no mortality or significant toxic effects such as reductions in food intake, body weight, relevant biochemical parameters and target organ weights were observed in the BCMA CAR T-cell-treated groups. Compared to the model group, restorative changes in clinical signs and clinicopathology indicating therapeutic effects were seen in the BCMA CAR T-cell-treated groups. Human-derived cytokines interleukin-2 (IL-2), IL-4, IL-6, IL-12, IL-10, tumor necrosis factor α (TNF-α), and interferon-γ (IFN-γ) could be detected in all cancer cell-bearing mice by cytokine level measurement. IFN-γ levels showed a geometric increase due to the graft versus host disease (GVHD) response induced in the mice, while the levels of the other cytokines did not show significant changes. Histopathological examination indicated that the BCMA CAR T-cell treatment groups showed mixed cellular infiltration of human-derived T cells, cancer cells, and inflammatory cells in several target organs including the liver, spleen, lung, and kidney, and some of them showed mild tissue damage, but the number of the animals and the severity of damage were significantly less than those of the T-cell control group as well as the model group. The results of the tissue distribution study showed that BCMA CAR T cells were mainly concentrated in the kidney, lung, bone marrow and the related immune organs/tissues, and the distribution of BCMA CAR T cells was highly consistent with that of MM cells, suggesting that BCMA CAR T cells could follow the cancer cells during metastatic targeting of the tissues.
The present study demonstrated a low toxicity of BCMA CAR T-cell injection, with manageable side effects and good anticancer activity and without observable adverse effects. This study provides data to support future clinical studies of BCMA CAR T-cell injection for MM. | [
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10.1056/NEJMOA2303379/SUPPL_FILE/NEJMOA2303379_DATA-SHARING.PDF
10.1038/s41591-022-02182-7
10.1182/BLOOD-2021-151672
10.1007/S40291-023-00673-Y
10.1136/jitc-2021-003486
10.1007/S40291-024-00723-Z/METRICS
10.1182/blood.2020008936
10.1200/JCO.2020.38.15_SUPPL.8504
10.1182/BLOOD-2021-146518 | [
"Guo",
"Wu",
"Li",
"Liang",
"Dai",
"Zhang",
"Dai",
"Zhang",
"Wen",
"Yang"
] | [
"Division of Life Science and State Key Lab of Molecular Neuroscience, Hong Kong University of Science and Technology, Hong Kong, Hong Kong SAR, China.\nGuangzhou Bay Area Institute of Biomedicine, Guangdong Lewwin Pharmaceutical Research Institute Co.,Ltd., Guangdong Provincial Key Laboratory of Drug Non-Clinical Evaluation and Research, Guangdong Engineering Research Center for Innovative Drug Evaluation and Research, Guangzhou, China.\nGuangdong Engineering Research Center for Cellular and Genetic Therapy Innovative Drugs, Shenzhen, China.",
"Guangzhou Bay Area Institute of Biomedicine, Guangdong Lewwin Pharmaceutical Research Institute Co.,Ltd., Guangdong Provincial Key Laboratory of Drug Non-Clinical Evaluation and Research, Guangdong Engineering Research Center for Innovative Drug Evaluation and Research, Guangzhou, China.\nCollege of Pharmacy, Guilin Medical University, Guilin, China.",
"Guangdong Engineering Research Center for Cellular and Genetic Therapy Innovative Drugs, Shenzhen, China.\nShenzhen Pregene Biopharma Company Ltd., Research and Development (R&D) Department, Shenzhen, China.",
"Division of Life Science and State Key Lab of Molecular Neuroscience, Hong Kong University of Science and Technology, Hong Kong, Hong Kong SAR, China.",
"Guangzhou Bay Area Institute of Biomedicine, Guangdong Lewwin Pharmaceutical Research Institute Co.,Ltd., Guangdong Provincial Key Laboratory of Drug Non-Clinical Evaluation and Research, Guangdong Engineering Research Center for Innovative Drug Evaluation and Research, Guangzhou, China.\nGuangdong Engineering Research Center for Cellular and Genetic Therapy Innovative Drugs, Shenzhen, China.",
"Guangzhou Bay Area Institute of Biomedicine, Guangdong Lewwin Pharmaceutical Research Institute Co.,Ltd., Guangdong Provincial Key Laboratory of Drug Non-Clinical Evaluation and Research, Guangdong Engineering Research Center for Innovative Drug Evaluation and Research, Guangzhou, China.\nGuangdong Engineering Research Center for Cellular and Genetic Therapy Innovative Drugs, Shenzhen, China.",
"Guangzhou Bay Area Institute of Biomedicine, Guangdong Lewwin Pharmaceutical Research Institute Co.,Ltd., Guangdong Provincial Key Laboratory of Drug Non-Clinical Evaluation and Research, Guangdong Engineering Research Center for Innovative Drug Evaluation and Research, Guangzhou, China.\nGuangdong Engineering Research Center for Cellular and Genetic Therapy Innovative Drugs, Shenzhen, China.",
"Guangzhou Bay Area Institute of Biomedicine, Guangdong Lewwin Pharmaceutical Research Institute Co.,Ltd., Guangdong Provincial Key Laboratory of Drug Non-Clinical Evaluation and Research, Guangdong Engineering Research Center for Innovative Drug Evaluation and Research, Guangzhou, China.\nGuangdong Engineering Research Center for Cellular and Genetic Therapy Innovative Drugs, Shenzhen, China.",
"Guangzhou Bay Area Institute of Biomedicine, Guangdong Lewwin Pharmaceutical Research Institute Co.,Ltd., Guangdong Provincial Key Laboratory of Drug Non-Clinical Evaluation and Research, Guangdong Engineering Research Center for Innovative Drug Evaluation and Research, Guangzhou, China.\nGuangdong Engineering Research Center for Cellular and Genetic Therapy Innovative Drugs, Shenzhen, China.",
"Division of Life Science and State Key Lab of Molecular Neuroscience, Hong Kong University of Science and Technology, Hong Kong, Hong Kong SAR, China.\nGuangzhou Bay Area Institute of Biomedicine, Guangdong Lewwin Pharmaceutical Research Institute Co.,Ltd., Guangdong Provincial Key Laboratory of Drug Non-Clinical Evaluation and Research, Guangdong Engineering Research Center for Innovative Drug Evaluation and Research, Guangzhou, China.\nGuangdong Engineering Research Center for Cellular and Genetic Therapy Innovative Drugs, Shenzhen, China."
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39605616 | 199 | Cellular behavior analysis from live-cell imaging of TCR T cell-cancer cell interactions. | T cell therapies, such as chimeric antigen receptor (CAR) T cells and T cell receptor (TCR) T cells, are a growing class of anti-cancer treatments. However, expansion to novel indications and beyond last-line treatment requires engineering cells' dynamic population behaviors. Here we develop the tools for | [
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] | 2024-11-28 | 47 | 39605616 | [
"T cell receptor",
"T cells",
"T cell therapies",
"anti-cancer treatments",
"chimeric antigen receptor",
"novel indications",
"engineering cells dynamic population behaviors",
"last-line treatment",
"CAR",
"(TCR) T cells",
"TCR",
"expansion",
"a growing class",
"the tools",
"we"
] | [] | 0 | 10.1101/2024.11.19.624390
10.5281/zenodo.7646429 | [
"Verma",
"Yu",
"Bachl",
"Lopez",
"Schwartz",
"Moen",
"Kale",
"Ching",
"Miller",
"Dougherty",
"Pao",
"Graf",
"Ward",
"Jena",
"Marson",
"Carnevale",
"Van Valen",
"Engelhardt"
] | [
"Institute of Data Science and Biotechnology, Gladstone Institutes, San Francisco, CA, USA.",
"Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA, USA.",
"School of Medicine, University of California, San Francisco, San Francisco,CA, USA.\nGladstone-UCSF Institute of Genomic Immunology, San Francisco, CA, USA.",
"School of Medicine, Stanford University, Stanford, California, USA.\nDepartment of Biomedical Data Science, Stanford University, Stanford, CA, USA.",
"Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA, USA.",
"Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA, USA.",
"School of Medicine, University of California, San Francisco, San Francisco,CA, USA.\nGladstone-UCSF Institute of Genomic Immunology, San Francisco, CA, USA.",
"School of Medicine, University of California, San Francisco, San Francisco,CA, USA.\nGladstone-UCSF Institute of Genomic Immunology, San Francisco, CA, USA.",
"Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA, USA.",
"Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA, USA.",
"Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA, USA.",
"Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA, USA.",
"Gladstone-UCSF Institute of Genomic Immunology, San Francisco, CA, USA.",
"Stem Cell and Regenerative Biology, Harvard University, Cambridge, Massachusetts, USA.",
"School of Medicine, University of California, San Francisco, San Francisco,CA, USA.\nGladstone-UCSF Institute of Genomic Immunology, San Francisco, CA, USA.",
"School of Medicine, University of California, San Francisco, San Francisco,CA, USA.\nGladstone-UCSF Institute of Genomic Immunology, San Francisco, CA, USA.",
"Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA, USA.",
"Institute of Data Science and Biotechnology, Gladstone Institutes, San Francisco, CA, USA.\nDepartment of Biomedical Data Science, Stanford University, Stanford, CA, USA."
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Subsets and Splits