Engineering solutions to design CAR-T cells

Abstract Engineering T cells with chimeric antigen receptors (CAR) to create CAR-T cells has emerged as promising immunotherapy. CAR-T cell-based therapies have shown clinical success in treating hematological malignancies. On contrary, CAR-T cells therapy for solid tumors has still a limited success and considerable effort is required for an improvement in the efficacy. This chapter will describe the developments in CAR structure (CARs generations) over the years. It will mainly focus on state-of-the-art engineering solutions proposed to enhance the therapeutic efficacy of CAR-T cells and on gene delivery strategies used to create CAR-T cells. Finally, some critical aspects for the clinical development of CAR-T cells will be discussed.