Armored human TREM2 CAR T cells are engineered to target TREM2-positive tumor-associated macrophages (TAMs) rather than tumor antigens. These cells locally secrete IL-12 through a tumor microenvironment–responsive biosensor, deplete TAMs, reprogram the tumor microenvironment, and promote tumor regression with no systemic toxicity reported. The approach aims to overcome TAM-mediated immunosuppression and broaden applicability to solid tumors. Uncertainty: outcomes beyond the reported preclinical context and comprehensive toxicity data are not specified in the provided content.
The suppressive tumor microenvironment (TME) severely limits CAR T cell therapy in solid tumors. Yagel et al. develop armored hTREM2 CAR T cells that target TREM2+ tumor-associated macrophages (TAMs) rather than tumor antigens and locally secrete interleukin-12 (IL-12) via a TME-responsive biosensor. These cells deplete TAMs, reprogram the TME, and drive tumor regression without systemic toxicity, offering a promising strategy for broad solid tumor therapy.