Department of Laboratory Medicine, Gongli Hospital, No. 219, Miaopu Road, Pudong, Shanghai, 200135, China.
TriArm Therapeutics Inc, Building 5, Niudun Road, Pudong New District, Shanghai, 201203, China.
Int Immunopharmacol. 2024 Jul 30;136:112379. doi: 10.1016/j.intimp.2024.112379. Epub 2024 Jun 3.
CAR-T therapy has demonstrated effectiveness in hematological malignancies and is now striding into solid tumor areas. One of the main roadblocks of CAR-T therapy is T cell exhaustion normally aroused by T cell terminal differentiation due to persistent contact with antigen in vivo or in vitro manufacturing process. T positions as the first, and pivotal step of naïve T cell differentiation to downstream memory and effector stages. Researchers highly seek to restrain CAR-T cells at the T stage during manufacture as T percentage in CAR-T products is strongly associated with better treatment response. We reviewed the recent strategies regarding CAR-T generation from aspects of starting source, manufacturing process, CAR assembly, transcription factor and metabolism regulation, etc.
嵌合抗原受体 T 细胞（CAR-T）疗法在血液恶性肿瘤中已显示出疗效，目前正在向实体瘤领域迈进。CAR-T 疗法的主要障碍之一是 T 细胞衰竭，这通常是由于 T 细胞在体内或体外制造过程中持续接触抗原而引起的 T 细胞终末分化引起的。T 细胞作为幼稚 T 细胞分化为下游记忆和效应阶段的第一步和关键步骤。研究人员非常希望在制造过程中使 CAR-T 细胞在 T 阶段失活，因为 CAR-T 产品中的 T 细胞百分比与更好的治疗反应密切相关。我们从起始源、制造过程、CAR 组装、转录因子和代谢调节等方面综述了 CAR-T 生成的最新策略。
