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

Oncology

Journal of Immunooncology

Author(s): Gross G, , , Eshhar Z,

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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. This article was published in Annu Rev Pharmacol Toxicol and referenced in Journal of Immunooncology

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