Redirection of T-cell effector functions for cancer therapy: bispecific antibodies and chimeric antigen receptors

Abstract

T cells are the most potent cells of the immune system; however, they fail in the immunosurveillance of tumors. In previous decades, scientists began studying methods to take advantage of T-cell potency in cancer therapy by redirecting them against tumors independently from the T-cell receptor-defined specificity. Among different approaches, the most promising are the use of bispecific antibodies and T-cell engineering to create chimeric antigen receptors. Bispecific antibodies, by simultaneously recognizing target antigen and an activating receptor on the surface of an immune effector cell, offer an opportunity to redirect immune effector cells to kill cancer cells. The other approach is the generation of chimeric antigen receptors by fusing extracellular antibodies to intracellular signaling domains. Chimeric antigen receptor-engineered T cells are able to specifically kill tumor cells in a MHC-independent way. The efficacy of these reagents in different formats has been clinically validated and will be presented here.