Lentiviral Vectors in CAR-T Cell Manufacturing: Biological Principles, Manufacturing Process, and Frontier Development

Abstract

Chimeric antigen receptor T cell (CAR-T) therapy, as the preeminent strategy in immunotherapy, has conferred benefits upon numerous cancer patients. Currently, there are six CAR-T therapies approved by the Food and Drug Administration (FDA), while the China National Medical Products Administration (NMPA) has approved three. The manufacturing process for CAR-T cells (CAR-Ts) entails using lentiviral vectors (LVVs), which are efficacious in transducing functional genes to both dividing and nondividing cells. Also, LVVs exert their capacity to integrate relatively large segments of DNA. Despite this fact, LVV-based CAR-Ts production can prove prohibitively expensive, and the yield of LVV can be further enhanced. In recent years, in-vivo generation of CAR-Ts has attracted significant attention since it stands to eliminate the ex-vivo isolation and activation process for T cells, thereby decreasing the cost and time involved in production. In view of this, this review summarizes the biological principles of LVVs and their manufacturing process, which encompasses lentiviral vector production, T cell isolation and activation, and CAR-Ts production. Additionally, the cutting-edge developments associated with LVVs are outlined herein, offering direction for the production of the next generation of CAR-Ts.