Chimeric antigen receptor-macrophages: Emerging next-generation cell therapy for brain cancer

Adoptive cell-based therapy utilizing chimeric antigen receptor (CAR)-T technology holds promise in the field of neuro-oncology. Significant progress has been made in enhancing both the efficacy and safety of CAR-T-cell therapies. However, challenges such as the multifaceted immunosuppressive impact of the tumor microenvironment and insufficient CAR-T-cell infiltration into brain tumor sites remain a major hurdles. Emerging novel approaches utilizing CAR-macrophages (CAR-MACs) show potent results for brain tumor immunotherapy. CAR-MACs localize to tumor sites more readily, increase immune cell infiltrates, and demonstrate high antitumor efficacy by effectively eliminating tumor cells through mechanisms such as phagocytosis or efferocytosis. This review discusses the current advancements in CAR-MAC cell therapies for brain cancer, followed by an overview of research on manufacturing CAR-MACs for clinical application. We further highlight the potential future applications of CAR-MACs in combinatory therapies in the treatment of brain tumors.