TGF‐β–responsive CAR‐T cells promote anti‐tumor immune function

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