In vivo CAR cell therapy: from bench to bedside

Chimeric antigen receptor T cell (CAR-T) therapy has emerged as a highly efficacious treatment for refractory and relapsed hematological malignancies in recent years. However, the complex manufacturing procedures, stringent logistical requirements, and protracted production timelines associated with autologous ex vivo CAR-T cells render them costly and inaccessible to many patients. In contrast, in vivo CAR-T therapy directly delivers CAR-encoding transgenes to endogenous T cells, reprogramming them in situ. This approach obviates the need for apheresis, ex vivo cell manufacturing, and lymphodepleting chemotherapy inherent in conventional CAR-T therapy. Consequently, in vivo CAR-T represents a more efficient and economical paradigm, transforming CAR-T from individualized cellular products towards truly "ready-to-use" therapeutics. This review summarizes the latest research progress in in vivo CAR cell therapies, spanning from bench to bedside, to provide insights for advancing their clinical translation.