From the Systems Pharmacology and Translational Therapeutics, Perelman School of Medicine, University of Pennsylvania.
Cancer J. 2023;29(1):28-33. doi: 10.1097/PPO.0000000000000636.
Genetically engineered chimeric antigen receptor (CAR) T-cell therapy leverages the ability of the immune system to eliminate tumors and redirects cytotoxic functions toward cells expressing specified tumor-restricted antigens. Although 6 CAR T-cell therapies have received Food and Drug Administration (FDA) approval for the treatment of many hematological malignancies, limitations involving T cell-intrinsic, T cell-extrinsic, and therapeutic factors remain in the treatment of both liquid and solid tumors. Chimeric antigen receptor design, signals from the tumor microenvironment, tumor antigen escape mechanisms, and systemic inflammatory consequences of CAR T-cell infusion all influence the efficacy and feasibility of CAR T-cell therapy in different malignancies. Here, we review the core structure of the CAR, the evolution of different CAR generations, CAR T-cell therapy limitations, and current strategies being investigated to overcome the T cell-intrinsic, T cell-independent, and therapeutic barriers to successful CAR T-cell therapy.
基因工程嵌合抗原受体 (CAR) T 细胞疗法利用免疫系统消除肿瘤的能力，并将细胞毒性功能重定向到表达特定肿瘤限制性抗原的细胞。尽管已有 6 种 CAR T 细胞疗法获得美国食品和药物管理局 (FDA) 批准，用于治疗多种血液系统恶性肿瘤，但在治疗液体和实体肿瘤方面，仍存在涉及 T 细胞内在、T 细胞外在和治疗因素的局限性。嵌合抗原受体设计、肿瘤微环境中的信号、肿瘤抗原逃逸机制以及 CAR T 细胞输注引起的全身炎症后果，都影响了 CAR T 细胞疗法在不同恶性肿瘤中的疗效和可行性。在这里，我们回顾了 CAR 的核心结构、不同 CAR 代的演变、CAR T 细胞疗法的局限性，以及目前正在研究的克服 T 细胞内在、T 细胞独立和治疗障碍以成功实施 CAR T 细胞疗法的策略。
