Reformation in chimeric antigen receptor based cancer immunotherapy: Redirecting natural killer cell.
Reformation in chimeric antigen receptor based cancer immunotherapy: Redirecting natural killer cell.
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基于嵌合抗原受体的癌症免疫疗法的改革：重定向自然杀伤细胞。
DOI：
10.1016/j.bbcan.2018.01.005
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发表时间：
2018
期刊：
影响因子：
--
通讯作者：
Zhang Jun
中科院分区：
文献类型：
--
作者：
Lin Chu;Zhang Jun
自然杀伤细胞（NK）是淋巴细胞的一个重要亚群，在宿主对癌症的免疫中起着关键作用。NK细胞具有mhc独立识别、短寿命和强大的细胞毒性，是嵌合抗原受体（CAR）工程癌症免疫治疗的有希望的候选者。由于NK细胞固有的生物学特性，CAR-NK可能在副作用更小、可及性更普遍方面优于CAR-T治疗，这可能成为基于car的癌症免疫治疗的重大变革。外周血NK细胞以及NK-92等NK细胞系中使用的car是确定抗原特异性的最重要工具。不同来源的NK细胞中使用的CARs结构各不相同，它们都经历了代际优化。CAR-NK的抗肿瘤作用已经在许多癌症的临床前试验中得到验证，包括血液恶性肿瘤和许多实体肿瘤，这为CAR-NK的潜在临床应用提供了证据。此外，本文还对CAR-NK在应用中面临的挑战进行了综述。尽管CAR-NK被认为是最有可能的“现成”产品之一，但在扩增和转导效率的提高以及潜在的安全问题的解决方面仍有待改进。针对CAR-NK癌症免疫治疗的未来发展，本文还强调了可能的应对策略和技术升级。
Natural killer (NK) cells are an important subset of lymphocytes which play a critical role in host immunity against cancers. With MHC-independent recognition, short lifespan and potent cytotoxicity, NK cells make a promising candidate for chimeric antigen receptor (CAR)-engineered cancer immunotherapy. Due to innate biological properties of NK cells, CAR-NK may outperform CAR-T therapy in terms of less side effects and more universal access, which may become a great reformation in CAR-based cancer immunotherapy. The CARs used in peripheral blood (PB) NK cells as well as NK cell line like NK-92 are the most important outfits defining antigenic specificity. The constructs of CARs used in NK cells from different sources vary, which all undergo generational optimization. The anti-tumor effects of CAR-NK have been validated in numerous preclinical trials for cancers, including hematologic malignancies and many solid tumors, which provide evidence for potential clinical application of CAR-NK. Additionally, this review concludes the challenges faced in the application of CAR-NK. Although CAR-NK is considered as one of the most possible “off-the-shelf” products, the improvement for the efficiency of expansion and transduction as well as the solution for underlying safety issues is still needed. Possible coping strategies for challenges and upgrades in techniques are also highlighted for future development in CAR-NK cancer immunotherapy.