Chimeric antigen receptor T cells engineered to secrete CD40 agonist antibodies enhance antitumor efficacy

Abstract Background Although chimeric antigen receptor (CAR)-T cell therapy has been remarkably successful for haematological malignancies, its efficacy against solid tumors is limited. The combination of CAR-T with immune checkpoint inhibitors (CPIs), such as PD-1, PD-L1, and CTLA-4 antibodies, a promising strategy enhancing the antitumor cells. However, because most patients acquire resistance to CPIs, investigating other strategies necessary further improve tumors. Recently, CD40 agonist antibodies showed potential by activating pathway. Results Based on piggyBac transposon system, rather than widely used viral vectors, we constructed meso3-CD40 targeting region III mesothelin (MSLN) that possessed ability secrete anti-CD40 antibodies. Compared meso3 cells, which did not antibody, cells secreted more cytokines had relatively higher proportion central memory T (T CM ) after stimulation target antigen. In addition, compared powerful cytotoxic effect at low effector-to-target ratio. More importantly, demonstrated activity was enhanced in human ovarian cancer xenograft model vivo. Conclusions conclusion, these results highlight anti-CD40-secreting generated nonviral vectors clinical improving therapies.