TGF-β-responsive CAR-T cells promote anti-tumor immune function.

A chimeric antigen receptor (CAR) that responds to transforming growth factor beta (TGF-beta) enables the engineering of T cells that convert this immunosuppressive cytokine into a potent T-cell stimulant. However, clinical translation of TGF-beta CAR-T cells for cancer therapy requires the ability to productively combine TGF-beta responsiveness with tumor-targeting specificity. Furthermore, the potential concern that contaminating, TGF-beta-producing regulatory T (Treg) cells may preferentially expand during TGF-beta CAR-T cell manufacturing and suppress effector T (Teff) cells demands careful evaluation. Here, we demonstrate that TGF-beta CAR-T cells significantly improve the anti-tumor efficacy of neighboring cytotoxic T cells. Furthermore, the introduction of TGF-beta CARs into mixed T-cell populations does not result in the preferential expansion of Treg cells, nor do TGF-beta CAR-Treg cells cause CAR-mediated suppression of Teff cells. These results support the utility of incorporating TGF-beta CARs in the development of adoptive T-cell therapy for cancer.