International Journal of Hematology

DOI: 10.1007/s12185-016-2039-6 Pages: 6-17

Biology and clinical application of CAR T cells for B cell malignancies

1. H. Lee Moffitt Cancer Center and Research Institute, Department of Blood and Marrow Transplantation

2. Memorial Sloan Kettering Cancer Center, Center for Cell Engineering

Correspondence to:
Marco L. Davila
Tel: 813-745-7202
Email: marco.davila@moffitt.org

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Abstract

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.

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