Advancing immunotherapy with innovations in CAR-M engineering for cancer treatment.

Chimeric antigen receptor macrophage (CAR-M) therapy is emerging as a promising immunotherapeutic strategy designed to overcome the limitations of T cell-based CAR therapies in solid tumors. However, CAR-T cells have shown limited efficacy in solid tumors due to poor tumor penetration and strong immunosuppressive signals in the tumor microenvironment (TME). CAR-M therapy has emerged as a promising alternative that may overcome these limitations. CAR-Ms are engineered macrophages that detect tumor antigens, enabling their accumulation in solid tumors where they destroy cancer cells by phagocytosis. Unlike CAR-T cells, CAR-Ms can remodel the TME and initiate innate and adaptive immune responses with lower risk of cytokine release syndrome (CRS). This review presents current approaches for engineering CAR-Ms and discusses how they engage tumor antigens within the TME. We also summarize recent advances in CAR-M delivery systems and functional design and highlight the status of clinical and preclinical studies evaluating CAR-M-based therapies. Despite remaining limitations, CAR-M therapy provides a compelling platform for solid tumor immunotherapy and is likely to play an expanding role in future cancer treatment.