In vivo CAR-T cell therapy: New breakthroughs for cell-based tumor immunotherapy

Chimeric antigen receptor (CAR)-T cell immunotherapy represents an evolutionary advance in the treatment of cancer, yet it faces challenges such as manufacturing complexity, high cost, and time-consuming process. In recent years, the strategy of in vivo CAR-T cell therapy is emerging as a promising approach to improve anti-tumor effectiveness and safety. Briefly, T cells are genetically modified to express CAR protein directly in the body by delivery of vectors. With the continuous optimization of gene delivery systems, gene editing technologies and CAR structures, advancements in in vivo CAR-T therapies have notably enhanced safety, effectiveness, and application in clinical settings. Here, we review the key platforms of in vivo gene delivery and the progress of in vivo CAR-T cell therapy for cancers. We discuss the challenges of in vivo CAR-T cell therapy, such as safety issues of gene delivery, the persistence and function of CAR-T cell, and the immunosuppressive microenvironment in solid tumors.