New power in cancer immunotherapy: the rise of chimeric antigen receptor macrophage (CAR-M).

Chimeric antigen receptor (CAR) therapy represents an innovative form of targeted treatment that employs genetically engineered effector cells to selectively target tumor cells. CAR-T immunotherapy, which uses T cells as effector cells, has demonstrated remarkable efficacy in hematological malignancies. However, its clinical application in solid tumors remains limited due to challenges such as poor tumor infiltration, cytokine release syndrome (CRS), neurotoxicity, off-target effects, and other adverse events. To address these limitations, CAR-engineered natural killer (CAR-NK) cells and macrophages (CAR-M) have been developed. Macrophages, as crucial components of innate and adaptive immunity, exhibit superior tumor microenvironment infiltration and long-term persistence, making them a promising tool for next-generation cancer immunotherapy. This review highlights the construction strategies and preclinical and clinical studies of CAR-M, comprehensively introduces the anti-tumor mechanisms, discusses their advantages and disadvantages compared with other CAR-engineered effector cells, and explores the challenges and prospects for CAR-M in treating solid tumors.