دورية أكاديمية
Deletion of CD38 enhances CD19 chimeric antigen receptor T cell function.
| العنوان: | Deletion of CD38 enhances CD19 chimeric antigen receptor T cell function. |
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| المؤلفون: | Veliz K; Center for Cellular Immunotherapies, University of Pennsylvania, Philadelphia, PA 19104, USA., Shen F; Center for Cellular Immunotherapies, University of Pennsylvania, Philadelphia, PA 19104, USA., Shestova O; Center for Cellular Immunotherapies, University of Pennsylvania, Philadelphia, PA 19104, USA., Shestov M; Center for Cellular Immunotherapies, University of Pennsylvania, Philadelphia, PA 19104, USA., Shestov A; Center for Cellular Immunotherapies, University of Pennsylvania, Philadelphia, PA 19104, USA., Sleiman S; Center for Cellular Immunotherapies, University of Pennsylvania, Philadelphia, PA 19104, USA., Hansen T; Center for Cellular Immunotherapies, University of Pennsylvania, Philadelphia, PA 19104, USA., O'Connor RS; Center for Cellular Immunotherapies, University of Pennsylvania, Philadelphia, PA 19104, USA.; Parker Institute for Cancer Immunotherapy, University of Pennsylvania, Philadelphia, PA 19104, USA., Gill S; Center for Cellular Immunotherapies, University of Pennsylvania, Philadelphia, PA 19104, USA.; Cell Therapy and Transplant Program, Division of Hematology-Oncology and Abramson Cancer Center, University of Pennsylvania, Philadelphia, PA 19104, USA. |
| المصدر: | Molecular therapy. Oncology [Mol Ther Oncol] 2024 May 24; Vol. 32 (2), pp. 200819. Date of Electronic Publication: 2024 May 24 (Print Publication: 2024). |
| نوع المنشور: | Journal Article |
| اللغة: | English |
| بيانات الدورية: | Publisher: Elsevier Inc Country of Publication: United States NLM ID: 9918752083706676 Publication Model: eCollection Cited Medium: Print ISSN: 2950-3299 (Print) Linking ISSN: 29503299 NLM ISO Abbreviation: Mol Ther Oncol Subsets: PubMed not MEDLINE |
| أسماء مطبوعة: | Original Publication: [New York] : Elsevier Inc., [2024]- |
| مستخلص: | Cell surface molecules transiently upregulated on activated T cells can play a counter-regulatory role by inhibiting T cell function. Deletion or blockade of such immune checkpoint receptors has been investigated to improve the function of engineered immune effector cells. CD38 is upregulated on activated T cells, and although there have been studies showing that CD38 can play an inhibitory role in T cells, how it does so has not fully been elucidated. In comparison with molecules such as PD1, CTLA4, LAG3, and TIM3, we found that CD38 displays more sustained and intense expression following acute activation. After deleting CD38 from human chimeric antigen receptor (CAR) T cells, we showed relative resistance to exhaustion in vitro and improved anti-tumor function in vivo . CD38 is a multifunctional ectoenzyme with hydrolase and cyclase activities. Reintroduction of CD38 mutants into T cells lacking CD38 provided further evidence supporting the understanding that CD38 plays a crucial role in producing the immunosuppressive metabolite adenosine and utilizing nicotinamide adenine dinucleotide (NAD) in human T cells. Taken together, these results highlight a role for CD38 as an immunometabolic checkpoint in T cells and lead us to propose CD38 deletion as an additional avenue for boosting CAR T cell function. Competing Interests: S.G. has patents related to CAR therapy with royalties paid from Novartis to the University of Pennsylvania. S.G. is a scientific cofounder and holds equity in Interius Biotherapeutics and Carisma Therapeutics. S.G. is a scientific advisor to Carisma, Cartography, Currus, Interius, Kite, NKILT, Mission Bio, and Vor Bio. (© 2024 The Author(s).) |
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| فهرسة مساهمة: | Keywords: CD38 enzyme; T cell exhaustion; cyclic-ADP ribose; metabolic reprogramming |
| تواريخ الأحداث: | Date Created: 20240624 Latest Revision: 20240625 |
| رمز التحديث: | 20240625 |
| مُعرف محوري في PubMed: | PMC11193011 |
| DOI: | 10.1016/j.omton.2024.200819 |
| PMID: | 38912091 |
| قاعدة البيانات: | MEDLINE |
| تدمد: | 2950-3299 |
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| DOI: | 10.1016/j.omton.2024.200819 |