In 2017, the United States Food and Drug Administration (FDA) granted the inaugural approval of chimeric antigen receptor T cell (CAR-T) therapy, marking the advent of a new era in cancer immunotherapy. However, the conventional ex vivo CAR‑T cell manufacturing workflow is complex and time consuming, resulting not only in high treatment costs and limited patient access, but also in effector differentiation of T cells and upregulation of exhaustion markers during prolonged in vitro expansion, which may impair the durability and antitumor activity of the cell product and reduce therapeutic efficacy. To enhance the efficacy and accessibility of CAR-T therapy, the strategy of in vivo generation of CAR cells has emerged as a prominent research focus, notwithstanding substantial technical challenges and its broad prospects. This review systematically summarizes the latest advances, technical challenges, and future trends of in vivo CAR-T therapy, with an emphasis on CAR mRNA molecular design, structural modifications, advancements in gene delivery technologies, and clinical applications, aiming to provide a comprehensive reference for related research.
Li et al. (Thu,) studied this question.