Biology and clinical application of CAR T cells for B cell malignancies.
Chimeric antigen receptor (CAR)-modified T cells have generated broad interest in oncology following a series of dramatic clinical successes in patients with chemorefractory B cell malignancies. CAR therapy now appears to be on the cusp of regulatory approval as a cell-based immunotherapy. We review here the T cell biology and cell engineering research that led to the development of second generation CARs, the selection of CD19 as a CAR target, and the preclinical studies in animal models that laid the foundation for clinical trials targeting CD19+ malignancies. We further summarize the status of CD19 CAR clinical therapy for non-Hodgkin lymphoma and B cell acute lymphoblastic leukemia, including their efficacy, toxicities (cytokine release syndrome, neurotoxicity and B cell aplasia) and current management in humans. We conclude with an overview of recent pre-clinical advances in CAR design that argues favorably for the advancement of CAR therapy to tackle other hematological malignancies as well as solid tumors.
Department of Blood and Marrow Transplantation, H. Lee Moffitt Cancer Center and Research Institute, 12902 Magnolia Drive, Tampa, FL, 33612, USA. marco.davila@moffitt.org.
Marco L
ML
Davila
Center for Cell Engineering, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
Michel
M
Sadelain
D000818:Animals; D018941:Antigens, CD19; D060846:Cell Engineering / Q000379:methods; D006801:Humans; D007167:Immunotherapy / Q000379:methods*; D015448:Leukemia, B-Cell / Q000628:therapy*; D016393:Lymphoma, B-Cell / Q000628:therapy*; D013601:T-Lymphocytes / Q000276:immunology*
D018941:Antigens, CD19
Adoptive T cell therapy; CD19; Chimeric antigen receptor; Immunotherapy; T cell engineering