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 CAR T 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 CAR T 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 CAR T cells through genetic engineering addresses these limitations and improves the antitumor efficacy of CAR T cell therapy in pre-clinical models.
Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
Janneke E
JE
Jaspers
Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA; Center for Cell Engineering, Memorial Sloan Kettering Cancer Center, New York, NY, USA; Molecular Pharmacology & Chemistry Program, Memorial Sloan Kettering Cancer Center, New York, NY, USA. Electronic address: brentjer@mskcc.org.
Renier J
RJ
Brentjens
D000818:Animals; D006801:Humans; D007167:Immunotherapy; D009369:Neoplasms / Q000276:immunology / Q000628:therapy*; D011948:Receptors, Antigen, T-Cell / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology*
D011948:Receptors, Antigen, T-Cell
Armored CAR T cells; Chimeric antigen receptor; Costimulation; Cytokines; Genetic engineering; Tumor microenvironment