CAR-T（CAR-T）细胞疗法在非肿瘤性疾病中的应用
Chimeric antigen receptor T (CAR-T) cell therapy in non-oncological diseases.
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
理解 CAR-T 细胞与肿瘤的相互作用：为成功的临床结局铺平道路
英文原题：Understanding CAR T cell-tumor interactions: Paving the way for successful clinical outcomes.
查看英文原题
Understanding CAR T cell-tumor interactions: Paving the way for successful clinical outcomes.
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中文摘要
自5年前获批以来，嵌合抗原受体（CAR）T细胞在血液系统恶性肿瘤的日常临床实践和治疗中已占据重要地位，尽管其应用仍面临诸多挑战，例如因疾病耐药或复发导致的CAR-T 细胞长期疗效有限。在简要概述CAR-T 细胞及其获批、治疗成功和持续存在的局限性之后，本综述讨论了关于CAR-T 细胞激活、其扩增与持久性、其细胞毒性机制，以及CAR设计和/或肿瘤内在因素如何影响这些功能的已知信息。本综述还探讨了细胞因子在CAR-T 细胞相关毒性中的作用及其对CAR-T 细胞功能的影响。此外，我们讨论了几种耐药机制，包括CAR治疗实体瘤相关的障碍。最后，我们对进一步优化CAR并改善临床结局的下一代策略进行了未来展望。
展开英文摘要原文
Since their approval 5 years ago, chimeric antigen receptor (CAR) T cells have gained great importance in the daily clinical practice and treatment of hematological malignancies, although many challenges to their use remain, such as limited long-term CAR T cell efficacy due to disease resistance or recurrence.
After a brief overview of CAR T cells, their approval, therapeutic successes, and ongoing limitations, this review discusses what is known about CAR T cell activation, their expansion and persistence, their mechanisms of cytotoxicity, and how the CAR design and/or tumor-intrinsic factors influence these functions. This review also examines the role of cytokines in CAR T cell-associated toxicity and their effects on CAR T cell function.
Furthermore, we discuss several resistance mechanisms, including obstacles associated with CAR treatment of solid tumors.
Finally, we provide a future outlook on next-generation strategies to further optimize CARs and improve clinical outcomes.
论文信息
- 作者
- Korell F、Berger TR、Maus MV
- 第一作者单位
- Cellular Immunotherapy Program, Massachusetts General Hospital Cancer Center, Charlestown, MA, USA; Harvard Medical School, Boston, MA, USA; Broad Institute of Harvard University and Massachusetts Institute of Technology, Cambridge, MA, USA.United States
- 通讯作者单位
- Cellular Immunotherapy Program, Massachusetts General Hospital Cancer Center, Charlestown, MA, USA; Harvard Medical School, Boston, MA, USA; Broad Institute of Harvard University and Massachusetts Institute of Technology, Cambridge, MA, USA. Electronic address: mvmaus@mgh.harvard.edu.United States
- 文献类型
- 综述 · 非美国政府资助研究
- 期刊
- Med (New York, N.Y.)2022 Aug 12
- 原文标识
- PubMed 35963235 · DOI 10.1016/j.medj.2022.05.001