Given the central role in T cell repression, attempts to counteract TGF-β were early undertaken during CAR development; application of TGF-β blocking antibodies augment antitumor activity.209,210 T cells equipped with a mutant TGF-β receptor gained superior activity and survival in the presence of TGF-β.211–213 Coexpressed with the CAR, a recombinant dominant-negative (DN) receptor sequesters TGF-β from the environment to protect the CAR T cell from repression.214 A clinical trial currently explores the benefit of TGF-β DN receptor while targeting prostate cancer (NCT 03089203). Here, TGFB1 is linked to prostate carcinoma.