打破免疫抑制屏障：一种保持原始 M1 表型优势的装甲型 CAR-M 生物技术可挽救抗肿瘤免疫

Chimeric antigen receptor macrophages (CAR-Ms) hold promise for solid tumor immunotherapy, but their efficacy is limited by tumor microenvironment (TME)-driven M2 polarization. Current strategies rely on antigen-dependent activation or in vitro priming, which fail to sustain the M1 phenotype in the immunosuppressive TME. In this research article, we developed a TME-regulated CAR-M (TMER CAR-M) biotechnology by integrating an original M1 phenotype dominance into an active CAR-M (ACT CAR-M) platform.

In tumor models, TMER CAR-M remodeled the TME, enhanced CD4+ and CD8+ T cell infiltration, increased the proportion of natural killer cells, reduced the frequency of regulatory T cells (Tregs) and myeloid-derived suppressor cells, effectively reversed the immunosuppressive state, and inhibited tumor growth in vivo. Crucially, human primary armored TMER CAR-M could effectively resist M2 reprogramming and reshape M2 macrophages.

In conclusion, an armored TMER CAR-M biotechnology with the original M1 phenotype dominance overcomes TME immunosuppression through two mechanisms, including autonomous M1 maintenance and M2 reprogramming without antigen stimulation. This biotechnology bridges a critical gap in CAR-M therapy for solid tumors, offering a clinically translatable platform for immune-cold malignancies.