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Annual Review of Pharmacology and Toxicology

Volume 56, 2016

Therapeutic Potential of T Cell Chimeric Antigen Receptors (CARs) in Cancer Treatment: Counteracting Off-Tumor Toxicities for Safe CAR T Cell Therapy

Abstract

A chimeric antigen receptor (CAR) is a recombinant fusion protein combining an antibody-derived targeting fragment with signaling domains capable of activating T cells. Recent early-phase clinical trials have demonstrated the remarkable ability of CAR-modified T cells to eliminate B cell malignancies. This review describes the choice of target antigens and CAR manipulations to maximize antitumor specificity. Benefits and current limitations of CAR-modified T cells are discussed, with a special focus on the distribution of tumor antigens on normal tissues and the risk of on-target, off-tumor toxicities in the clinical setting. We present current methodologies for pre-evaluating these risks and review the strategies for counteracting potential off-tumor effects. Successful implementation of these approaches will improve the safety and efficacy of CAR T cell therapy and extend the range of cancer patients who may be treated.

Keyword(s): adoptive T cell therapy, cancer immunotherapy, CARs, chimeric antigen receptors, on/off-target effects, tumor antigens
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/content/journals/10.1146/annurev-pharmtox-010814-124844
2016-01-06
2024-04-18
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Therapeutic Potential of T Cell Chimeric Antigen Receptors (CARs) in Cancer Treatment: Counteracting Off-Tumor Toxicities for Safe CAR T Cell Therapy
Annual Review of Pharmacology and Toxicology 56, 59 (2016); https://doi.org/10.1146/annurev-pharmtox-010814-124844
/content/journals/10.1146/annurev-pharmtox-010814-124844
/content/journals/10.1146/annurev-pharmtox-010814-124844
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