Bioactive-material-programmed CAR-T cell living drug for augmented immunotherapy against tumors

The therapeutic efficacy of chimeric antigen receptor (CAR)-T cell therapy against solid tumors remains hindered by issues including physical barriers, the immunosuppressive tumor microenvironment (TME), and severe side effects. In response, bioactive-material-programmed CAR-T cells have emerged as a promising cancer treatment strategy that not only enhances the antitumor effects of T cells but also endows them with additional functional activities. In this review, the recent progress in engineered techniques for programming CAR-T cells against solid tumors is systematically introduced. We summarize the use of bioactive-material-programmed CAR-T cells for disrupting TME barriers by modulating the immunosuppressive microenvironment, thus avoiding the side effects. We further discuss the promises along with the challenges of bioactive-material-programmed CAR-T cells and CAR-T cell-based micro/nanorobots with concerns related to future clinical translation. This review offers a comprehensive overview of the advances in biomaterial-engineered CAR-T cells, potentially contributing to the development of therapeutic CAR-T cell-based living cell drugs.