In-Vivo Induced CAR-T Cell for the Potential Breakthrough to Overcome the Barriers of Current CAR-T Cell Therapy

Chimeric antigen receptor T cell (CAR-T cell) therapy has shown impressive success in the treatment of hematological malignancies, but the systemic toxicity and complex manufacturing process of current autologous CAR-T cell therapy hinder its broader applications. Universal CAR-T cells have been developed to simplify the production process through isolation and editing of allogeneic T cells from healthy persons, but the allogeneic CAR-T cells have recently encountered safety concerns, and clinical trials have been halted by the FDA. Thus, there is an urgent need to seek new ways to overcome the barriers of current CAR-T cell therapy. In-vivo CAR-T cells induced by nanocarriers loaded with CAR-genes and gene-editing tools have shown efficiency for regressing leukemia and reducing systemic toxicity in a mouse model. The in-situ programming of autologous T-cells avoids the safety concerns of allogeneic T cells, and the manufacture of nanocarriers can be easily standardized. Therefore, the in-vivo induced CAR-T cells can potentially overcome the abovementioned limitations of current CAR-T cell therapy. Here, we provide a review on CAR structures, gene-editing tools, and gene delivery techniques applied in immunotherapy to help design and develop new in-vivo induced CAR-T cells.