Harnessing chimeric antigen receptor macrophages against solid tumors

Macrophages are prevalent in multiple tumors and exhibit diverse and potent functional activities. Therapeutic reprogramming of macrophage phenotypes represents a promising strategy for cancer immunotherapy. Engineering chimeric antigen receptors (CARs) to endow macrophages with anti-tumor capacities demonstrated encouraging efficacy, particularly in enhancing tumor-targeted phagocytosis. Furthermore, CAR macrophages (CAR-Ms) orchestrate adaptive immunity through secreting pro-inflammatory cytokines and presenting tumor antigens, thereby activating cytotoxic T lymphocyte responses. These multifaceted properties establish CAR-Ms as potent immunotherapeutic agents against therapy-refractory solid malignancies. Herein, we delineate the design principles, recent research advances, and rational combination strategies of CAR-Ms, with particular emphasis on emerging clinical evidence from ongoing CAR-M trials. We also explore potential applications of CAR-Ms in non-tumorous diseases and forecast future trends based on CAR-T therapy evolution. CAR-M development, combined with emerging technologies, will generate new perspectives for advancing cancer immunotherapy.