دورية أكاديمية
Chimeric antigen receptor-induced antigen loss protects CD5.CART cells from fratricide without compromising on-target cytotoxicity.
العنوان: | Chimeric antigen receptor-induced antigen loss protects CD5.CART cells from fratricide without compromising on-target cytotoxicity. |
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المؤلفون: | Ma R; Center for Cell and Gene Therapy, Baylor College of Medicine, Texas Children's Hospital, Houston, TX 77030, USA; Graduate Program in Immunology and Microbiology, Baylor College of Medicine, Houston, TX 77030, USA; William T. Shearer Center for Human Immunobiology, Texas Children's Hospital, Houston, TX 77030, USA; Dan L. Duncan Comprehensive Cancer Center, Baylor College of Medicine, Houston, TX 77030, USA., Woods M; Center for Cell and Gene Therapy, Baylor College of Medicine, Texas Children's Hospital, Houston, TX 77030, USA., Burkhardt P; Center for Cell and Gene Therapy, Baylor College of Medicine, Texas Children's Hospital, Houston, TX 77030, USA; Graduate Program in Immunology and Microbiology, Baylor College of Medicine, Houston, TX 77030, USA., Crooks N; Center for Cell and Gene Therapy, Baylor College of Medicine, Texas Children's Hospital, Houston, TX 77030, USA., van Leeuwen DG; Center for Cell and Gene Therapy, Baylor College of Medicine, Texas Children's Hospital, Houston, TX 77030, USA; Graduate Program in Immunology and Microbiology, Baylor College of Medicine, Houston, TX 77030, USA., Shmidt D; Center for Cell and Gene Therapy, Baylor College of Medicine, Texas Children's Hospital, Houston, TX 77030, USA., Couturier J; Center for Cell and Gene Therapy, Baylor College of Medicine, Texas Children's Hospital, Houston, TX 77030, USA., Chaumette A; Center for Cell and Gene Therapy, Baylor College of Medicine, Texas Children's Hospital, Houston, TX 77030, USA., Popat D; Center for Cell and Gene Therapy, Baylor College of Medicine, Texas Children's Hospital, Houston, TX 77030, USA., Hill LC; Center for Cell and Gene Therapy, Baylor College of Medicine, Texas Children's Hospital, Houston, TX 77030, USA; Dan L. Duncan Comprehensive Cancer Center, Baylor College of Medicine, Houston, TX 77030, USA., Rouce RH; Center for Cell and Gene Therapy, Baylor College of Medicine, Texas Children's Hospital, Houston, TX 77030, USA., Thakkar S; Center for Cell and Gene Therapy, Baylor College of Medicine, Texas Children's Hospital, Houston, TX 77030, USA., Orozco AF; Center for Cell and Gene Therapy, Baylor College of Medicine, Texas Children's Hospital, Houston, TX 77030, USA., Carisey AF; William T. Shearer Center for Human Immunobiology, Texas Children's Hospital, Houston, TX 77030, USA., Brenner MK; Center for Cell and Gene Therapy, Baylor College of Medicine, Texas Children's Hospital, Houston, TX 77030, USA; Graduate Program in Immunology and Microbiology, Baylor College of Medicine, Houston, TX 77030, USA; Dan L. Duncan Comprehensive Cancer Center, Baylor College of Medicine, Houston, TX 77030, USA., Mamonkin M; Center for Cell and Gene Therapy, Baylor College of Medicine, Texas Children's Hospital, Houston, TX 77030, USA; Graduate Program in Immunology and Microbiology, Baylor College of Medicine, Houston, TX 77030, USA; Department of Pathology and Immunology, Baylor College of Medicine, Houston, TX 77030, USA; Dan L. Duncan Comprehensive Cancer Center, Baylor College of Medicine, Houston, TX 77030, USA. Electronic address: mamonkin@bcm.edu. |
المصدر: | Cell reports. Medicine [Cell Rep Med] 2024 Jul 16; Vol. 5 (7), pp. 101628. Date of Electronic Publication: 2024 Jul 09. |
نوع المنشور: | Journal Article |
اللغة: | English |
بيانات الدورية: | Publisher: Cell Press Country of Publication: United States NLM ID: 101766894 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 2666-3791 (Electronic) Linking ISSN: 26663791 NLM ISO Abbreviation: Cell Rep Med Subsets: MEDLINE |
أسماء مطبوعة: | Original Publication: [Cambridge, MA] : Cell Press, [2020]- |
مواضيع طبية MeSH: | CD5 Antigens*/metabolism , Receptors, Chimeric Antigen*/metabolism , Receptors, Chimeric Antigen*/immunology, Humans ; Cytotoxicity, Immunologic ; T-Lymphocytes/immunology ; T-Lymphocytes/metabolism ; Immunotherapy, Adoptive/methods ; Animals ; Receptors, Antigen, T-Cell/metabolism ; Receptors, Antigen, T-Cell/immunology |
مستخلص: | Chimeric antigen receptor T cells (CART) targeting lymphocyte antigens can induce T cell fratricide and require additional engineering to mitigate self-damage. We demonstrate that the expression of a chimeric antigen receptor (CAR) targeting CD5, a prominent pan-T cell antigen, induces rapid internalization and complete loss of the CD5 protein on T cells, protecting them from self-targeting. Notably, exposure of healthy and malignant T cells to CD5.CART cells induces similar internalization of CD5 on target cells, transiently shielding them from cytotoxicity. However, this protection is short-lived, as sustained activity of CD5.CART cells in patients with T cell malignancies results in full ablation of CD5 + T cells while sparing healthy T cells naturally lacking CD5. These results indicate that continuous downmodulation of the target antigen in CD5.CART cells produces effective fratricide resistance without undermining their on-target cytotoxicity. Competing Interests: Declaration of interests M.M. and M.K.B. are co-founders of March Biosciences, have equity, and serve on the advisory board for March Biosciences. M.K.B. is a cofounder and equity holder in AlloVir, Inc. and Marker Therapeutics. M.K.B. has equity in Tessa Therapeutics Ltd. and March Biosciences and serves on advisory boards for Marker Therapeutics, Allogene, Walking Fish, Abintus, Tessa Therapeutics, Athenex, ONK Therapeutics, Coya Therapeutics, Triumvira, Adaptimmune, Vor Therapeutics, and TScan. M.M. serves on the scientific advisory board of NKILT and receives research support from Fate Therapeutics and honoraria from Amgen and Galapagos NV. L.C.H. provides consulting services to March Biosciences. M.M. and M.K.B. have patent applications and a granted patent related to this work. An up-to-date declaration of interests for the listed authors can be found at https://www.bcm.edu/academic-centers/cell-and-gene-therapy/research/disclosure-of-outside-interests. (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.) |
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فهرسة مساهمة: | Keywords: CAR; CD5; T cell fratricide; T cell malignancies; chimeric antigen receptor; clinical trials; fratricide; off-tumor toxicity |
المشرفين على المادة: | 0 (CD5 Antigens) 0 (Receptors, Chimeric Antigen) 0 (Receptors, Antigen, T-Cell) |
تواريخ الأحداث: | Date Created: 20240710 Date Completed: 20240717 Latest Revision: 20240816 |
رمز التحديث: | 20240816 |
مُعرف محوري في PubMed: | PMC11293353 |
DOI: | 10.1016/j.xcrm.2024.101628 |
PMID: | 38986621 |
قاعدة البيانات: | MEDLINE |
تدمد: | 2666-3791 |
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DOI: | 10.1016/j.xcrm.2024.101628 |