Development of CAR T cells designed to improve antitumor efficacy and safety

Chimeric antigen receptor (CAR) T cell therapy has shown promising efficacy against hematologic malignancies. Antitumor activity of CART cells, however, needs to be improved to increase therapeutic efficacy in both hematologic and solid cancers. Limitations to overcome are 'on-target, off-tumor' toxicity, antigen escape, short CART cell persistence, little expansion, trafficking to the tumor and inhibition of T cell activity by an inhibitory tumor microenvironment. Here we will discuss how optimizing the design of CART cells through genetic engineering addresses these limitations and improves the antitumor efficacy of CART cell therapy in pre-clinical models. Published by Elsevier Inc.