Fig. 3

Combinatorial strategy for therapeutic T cell that integrates activation signaling pathway and inhibitory signaling pathway. In the promotion of the activation signaling pathway, this design conformation of the modified-T cell can yield safer therapeutic function upon the safe platform, including the dual receptor engineering T cell and bifunctional molecules. In this system, the T cell that carry two receptors can engage the molecules and tumor surface antigens, and the bifunctional molecule can target T cells and cancer cells. On the other hand, blocking the inhibitory signaling pathway by adding some monoclonal antibodies, such as tremelimumab and nivolumab with specificity for CTLA-4 and PD-1, respectively, was also found to improve the efficacy and persistence of the infused CAR-T cell in vitro and in vivo