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血液系统恶性肿瘤与实体瘤中的 CAR NK 细胞治疗:障碍与克服挑战的策略

英文原题:CAR NK cell therapy in hematologic malignancies and solid tumors; obstacles and strategies to overcome the challenges.

查看英文原题

CAR NK cell therapy in hematologic malignancies and solid tumors; obstacles and strategies to overcome the challenges.

PubMed 2022/07/12(内容时间) Int Immunopharmacol Q1 · IF 5.6(JCR 2025)

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中文摘要

采用嵌合抗原受体(CAR)的过继细胞治疗(ACT),可改变安全细胞的靶向特异性,使其识别特定抗原,在癌症治疗中具有突出潜力。CAR-T 虽已成为突破性疗法,并在治疗人类恶性肿瘤方面取得前所未有的疗效,但制备流程复杂且昂贵、患者资格限制严格以及不良毒性等问题妨碍了其应用。与T细胞不同,自然杀伤(NK)细胞因不依赖主要组织相容性复合体(MHC)、寿命较短、可制备现货型免疫产品且具有强抗肿瘤效应,被视为合理替代方案并受到关注。本文更新综述CAR-T 和CAR-NK细胞的差异、CAR-NK设计的最新改进、NK细胞来源及CAR向NK细胞转导策略。此外,重点讨论CAR-NK治疗血液系统恶性肿瘤和实体瘤的已发表及正在进行的临床前与临床研究,并分析可行的解决方案,以改善CAR-NK细胞的持久性、功能、安全性及疗效,特别关注实体瘤。

展开英文摘要原文

Adoptive cell treatment (ACT) utilizing chimeric antigen receptors (CAR) diverts the specificity of safe cells against a target-specific antigen and portrays exceptional potential for cancer treatment. While CAR T cell treatment has risen as a breakthrough with unprecedented results within the therapeutic procedures of human malignancies, different deficiencies including challenging and costly generation processes, strict patient qualification criteria, and undesirable toxicity have ruined its application.

Unlike T cells, the application of natural killer (NK) cells has attracted consideration as a reasonable alternative owing to the major histocompatibility complex (MHC)-independency, shorter life expectancy, the potential to create an off-the-shelf immune product, and potent antitumor properties. In this article, we provide an updated review of the differences between CAR T and CAR NK cells, current enhancements in CAR NK design, the available sources for collecting NK cells, and strategies for the transduction step of the CARs to NK cells.

Furthermore, we focus on the published and ongoing preclinical and clinical studies of CAR NK treatment strategies both in hematologic malignancies and solid tumors.

We also discuss limitations and plausible solutions to improve the perseverance, function, safety, and efficacy of CAR NK cells with a special focus on solid tumors.

论文信息

作者
Baghery Saghchy Khorasani A、Yousefi AM、Bashash D
第一作者单位
Department of Hematology, School of Medical Sciences, Tarbiat Modares University, Tehran, Iran.Iran
通讯作者单位
Department of Hematology and Blood Banking, School of Allied Medical Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran. Electronic address: D.bashash@sbmu.ac.ir.Iran
文献类型
综述
期刊
International immunopharmacology2022 Sep
原文标识
PubMed 35839565 · DOI 10.1016/j.intimp.2022.109041