标题: CAR-T细胞在癌症中的治疗潜力以及抗肿瘤毒性的安全性 [打印本页] 作者: icartab 时间: 2016-1-27 14:04 标题: CAR-T细胞在癌症中的治疗潜力以及抗肿瘤毒性的安全性 Therapeutic Potential of T Cell Chimeric Antigen Receptors (CARs) in Cancer Treatment: Counteracting Off-Tumor Toxicities for Safe CAR T Cell Therapy.
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.
KEYWORDS:
CARs; adoptive T cell therapy; cancer immunotherapy; chimeric antigen receptors; on/off-target effects; tumor antigens