Revolution in Cell Therapy: In Vivo Chimeric-Antigen-Receptor-T-Cell Therapy Breakthroughs and Promises for the Future.

Chimeric-antigen-receptor (CAR)-T-cell therapy has achieved important results in the treatment of hematological tumors, but traditional CAR-T-cell therapy has the problems of complicated in vitro preparation processes, high cost, low T-cell function in patients, difficulty in multiple dosing, and limited treatment efficacy in solid tumors. In vivo CAR-T-cell therapy has emerged as needed. The CAR gene component is directly delivered to T cells in the host through the delivery system to achieve in situ reprogramming, avoids in vitro manipulation, and has important advantages in terms of the timeliness of treatment, economic feasibility, and persistence of treatment. This paper describes the current state of research on in vivo CAR-T-cell therapy, including the development of delivery systems and the application of CAR-T-cell therapy in treating hematological malignancies, solid tumors, autoimmune diseases, and infectious diseases, as well as discussions on efficient delivery, safety regulation, persistence and functional optimization, and overcoming the tumor microenvironment. It also explores innovative solutions, which hold promise for the future development of in vivo CAR-T-cell therapy, particularly in terms of technological breakthroughs, expansion of treatment indications, and industrialization.