Research Progress on Challenges in In Vivo CAR-T Cell Therapy

The emergence of chimeric antigen receptor (CAR) T-cell therapy heralds a paradigm shift in cancer immunotherapy. Different from in-vitro CAR-T products, in-vivo CAR-T engineering accomplishes in-situ reprogramming of endogenous T cells, making possible long-lasting anti-tumor cytotoxic activity, which is cost-effective in production and has immediate accessibility as an off-the-shelf product. However, challenges like low target specificity, immune suppression in the tumor microenvironment, treatment resistance, and safety concerns do impede its clinical translational application. This review summarizes the main CAR delivery vectors representative preclinical and clinical studies as well as new strategies to overcome current limitations with the purpose of facilitating the clinical development of this emerging therapy.