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嵌合抗原受体自然杀伤细胞:实体瘤免疫治疗的新见解(综述)

Chimeric antigen receptor-natural killer cells: Novel insight into immunotherapy for solid tumors (Review).

作者信息

Peng Xiaobo, Chen Ling, Chen Longpei, Wang Bin, Wang Yiran, Zhan Xianbao

机构信息

Department of Oncology, Changhai Hospital affiliated to Naval Military Medical University, Shanghai 200081, P.R. China.

出版信息

Exp Ther Med. 2021 Apr;21(4):340. doi: 10.3892/etm.2021.9771. Epub 2021 Feb 10.

Abstract

The chimeric antigen receptor (CAR) is an artificially modified fusion protein consisting of an extracellular antigen-binding domain, transmembrane domain and intracellular signalling domain. CAR-T therapy has demonstrated remarkable clinical efficacy in hematological malignancies. However, cytokine release syndrome and other side effects have hindered its application in solid tumors. CAR-natural killer (NK) cells have attracted broad attention due to their safety in clinical applications, their mechanism in recognising cancer cells and the abundance of its clinical specimens. Preclinical and clinical trials of human primary NK cells and NK-92 cell lines demonstrated that CAR-NK cells are able to fight haematological malignancies and solid tumors. However, the implication of CAR-NK cell therapy also has certain challenges, including the expansion and activation of primary NK cells , selection of CAR targets, survival time of CAR-NK cells , storage and transportation of NK cells, and efficiency of NK cell transduction. This review focuses on the latest progress of CAR-NK cells in the treatment of solid tumors.

摘要

嵌合抗原受体(CAR)是一种人工修饰的融合蛋白,由细胞外抗原结合域、跨膜域和细胞内信号域组成。CAR-T疗法在血液系统恶性肿瘤中已显示出显著的临床疗效。然而,细胞因子释放综合征和其他副作用阻碍了其在实体瘤中的应用。CAR-自然杀伤(NK)细胞因其临床应用的安全性、识别癌细胞的机制以及丰富的临床标本而受到广泛关注。对人原代NK细胞和NK-92细胞系的临床前和临床试验表明,CAR-NK细胞能够对抗血液系统恶性肿瘤和实体瘤。然而,CAR-NK细胞疗法的应用也存在一定挑战,包括原代NK细胞的扩增和激活、CAR靶点的选择、CAR-NK细胞的存活时间、NK细胞的储存和运输以及NK细胞转导效率。本综述重点关注CAR-NK细胞在实体瘤治疗中的最新进展。

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