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

Abstract

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.