Biology and clinical application of CAR T cells for B cell malignancies
- 4 June 2016
- journal article
- review article
- Published by Springer Science and Business Media LLC in International Journal of Hematology
- Vol. 104 (1), 6-17
- https://doi.org/10.1007/s12185-016-2039-6
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.Keywords
This publication has 64 references indexed in Scilit:
- The promise and potential pitfalls of chimeric antigen receptorsCurrent Opinion in Immunology, 2009
- Effector and Memory CTL DifferentiationAnnual Review of Immunology, 2007
- Jurkat T cells and development of the T-cell receptor signalling paradigmNature Reviews Immunology, 2004
- Cancer Patient T Cells Genetically Targeted to Prostate-Specific Membrane Antigen Specifically Lyse Prostate Cancer Cells and Release Cytokines in Response to Prostate-Specific Membrane AntigenNeoplasia, 1999
- Signals through T cell receptor-zeta chain alone are insufficient to prime resting T lymphocytes.The Journal of Experimental Medicine, 1995
- New simplified molecular design for functional T cell receptorEuropean Journal of Immunology, 1993
- Specific activation and targeting of cytotoxic lymphocytes through chimeric single chains consisting of antibody-binding domains and the gamma or zeta subunits of the immunoglobulin and T-cell receptors.Proceedings of the National Academy of Sciences of the United States of America, 1993
- Activation of T Cells by a Tyrosine Kinase Activation Domain in the Cytoplasmic Tail of CD3 εScience, 1992
- Identification of a murine monoclonal antibody specific for an allotypic determinant on mouse CD3European Journal of Immunology, 1991
- The cytoplasmic domain of the T cell receptor ζ chain is sufficient to couple to receptor-associated signal transduction pathwaysCell, 1991