Abstract: Chimeric antigen receptor (CAR)⁃T cell therapy has demonstrated remarkable success in the treatment of hematologic malignancies. However, currently approved CAR⁃T products are predominantly autologous, which face limitations including lengthy manufacturing processes, high costs, and the variability of product quality, restricting their broad clinical application. Universal CAR⁃T (UCAR⁃T) therapy, developed from healthy donor⁃derived T cells, through ex vivo modification and expansion, offer an "off⁃the⁃shelf" product that enable on⁃demand treatment, thereby overcoming the constraints of autologous CAR⁃T. Nevertheless, UCAR⁃T therapy remain challenged at complications including graft⁃versus⁃host disease (GvHD) and host⁃versus⁃graft reaction (HvG). This review summarizes recent progress on strategies to mitigate GvHD and HvG in UCAR⁃T therapy, including gene editing, non⁃gene⁃editing technologies, and optimal cell source selection.

Key words: Hematologic malignancies, CAR?T cell therapy, Universal CAR?T, Graft?versus?host disease, Host?versus?graft reaction