Chimeric antigen receptors designed to overcome transforming growth factor‐β‐mediated repression in the adoptive T‐cell therapy of solid tumors

Adoptive cell therapy with chimeric antigen receptor (CAR)‐engineered T cells produced lasting remissions in the treatment of advanced, so far refractory B‐cell malignancies; however, the elimination of solid tumors remains so far elusive. The low efficacy of CAR T cells is thought to be due to the immune‐repressive milieu within the tumor lesion, predominantly mediated by transforming growth factor‐β (TGF‐β) that represses effector T‐cell activities and drives differentiation towards regulatory T cells (Tregs). Seeking to boost antitumor immunity, TGF‐β is currently targeted by different means in pre‐clinical studies. While a recent clinical trial showed the utility of shielding CAR T cells from TGF‐β repression, further strategies in counteracting TGF‐β in the adoptive cell therapy warrant exploration. We here discuss the most recent advances in the field and draw future developments to make CAR T‐cell therapy more potent in the treatment of solid cancer.