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CAR-T细胞在癌症中的治疗潜力以及抗肿瘤毒性的安全性

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发表于 2016-1-27 13:54:14 | 显示全部楼层 |阅读模式
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

CAR-T细胞在癌症中的治疗潜力以及抗肿瘤毒性的安全性

嵌合抗原受体(CAR)是一种重组的融合蛋白,由抗体来源的目标片段与能激活T细胞的信号域组成。最近的早期阶段临床试验已经证明了CAR-T细胞具有显著的消除B细胞恶性肿瘤的能力。这篇评论描述了目标抗原的选择和CAR的操作,以最大限度地提高其抗肿瘤的特异性。我们讨论了CAR-T细胞的优势和目前的限制,主要集中在肿瘤抗原在正常组织上的分布,以及临床上靶向肿瘤和非靶向肿瘤毒性带来的风险。我们称述一些目前评估这些风险的方法,并且回顾能抵消潜在肿瘤毒性的一些策略。这些方法的成功实施,将提高CAR-T技术的安全性和有效性,并增大了治疗的癌症患者的范围。
关键词:
CAR;细胞疗法;肿瘤免疫治疗;嵌合抗原受体;靶向作用;肿瘤抗原
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