Generation of CAR-TSCM: CAR-T with super clutch

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_SCM 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_SCM stage during manufacture as T_SCM percentage in CAR-T products is strongly associated with better treatment response. We reviewed the recent strategies regarding CAR-T_SCM generation from aspects of starting source, manufacturing process, CAR assembly, transcription factor and metabolism regulation, etc.