Harnessing myeloid plasticity in CAR macrophages for solid tumor immunotherapy

Chimeric antigen receptor macrophages (CAR-Ms) are an emerging myeloid cell therapy designed to exploit the inherent plasticity of macrophages in solid tumors. By integrating antigen-specific recognition with macrophage-mediated phagocytosis, antigen presentation, and local immune remodeling, CAR-Ms coordinate tumor killing with reprogramming of the tumor microenvironment. Advances in CAR design, intracellular signaling, cellular platforms, and gene delivery have enabled preclinical evaluation in immunocompetent models and early clinical testing. CAR-Ms can enhance T cell and NK cell infiltration, promote antigen spreading, and sensitize tumors to immune checkpoint blockade. Early clinical studies, including HER2-targeted CT-0508, demonstrate feasible manufacturing, acceptable safety, tumor infiltration, and immune remodeling, though objective efficacy remains limited. Major challenges include maintaining antitumor polarization, persistence, scalable manufacturing, target selection, and safety control. Continued optimization of CAR-M design and exploitation of myeloid plasticity will be critical to realizing their potential as solid tumor immunotherapy platforms.