期刊
ANNUAL REVIEW OF PHARMACOLOGY AND TOXICOLOGY, VOL 56
卷 56, 期 -, 页码 59-+出版社
ANNUAL REVIEWS
DOI: 10.1146/annurev-pharmtox-010814-124844
关键词
adoptive T cell therapy; chimeric antigen receptors; CARs; cancer immunotherapy; tumor antigens; on/off-target effects
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.
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