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嵌合抗原受体自然杀伤(CAR-NK)细胞用于肿瘤治疗的开发与应用:现状、挑战与新兴治疗进展

英文原题:The development and application of chimeric antigen receptor natural killer (CAR-NK) cells for cancer therapy: current state, challenges and emerging therapeutic advances.

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The development and application of chimeric antigen receptor natural killer (CAR-NK) cells for cancer therapy: current state, challenges and emerging therapeutic advances.

PubMed 2024/12/04(内容时间) Exp Hematol Oncol Q1 · IF 17.5(JCR 2025)

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中文摘要

免疫治疗改变了癌症治疗格局,嵌合抗原受体(CAR)工程化T细胞(CAR-T)疗法成为治疗部分血液系统恶性肿瘤的重要方法。尽管CAR-T 疗效显著,严重不良反应限制了其应用范围,并促使研究者探索替代疗法。自然杀伤(NK)细胞具有先天细胞毒性,能杀伤靶细胞,且不像T细胞那样受主要组织相容性复合体(MHC)呈递肽特异性的限制,因此同样成为可行的免疫疗法。近期出现了一种结合CAR-T 持续成功经验与NK细胞灵活性的治疗策略,即CAR工程化NK(CAR-NK)细胞疗法。临床试验显示CAR-NK疗法具有良好疗效,且有害副作用较少。本综述简要概述NK细胞生物学的细胞和分子基础,以帮助理解CAR设计和制备的进展。文章重点介绍CAR-NK细胞开发的当前方法和策略,并探讨临床前及临床研究,回顾CAR-NK疗法已取得的进展、优势和固有挑战。随着CAR-NK细胞技术成熟,我们预计该疗法有望惠及更广泛癌症患者及其他疾病患者,并推动难治性和复发性癌症以及其他免疫介导疾病的治疗取得重要进展。

展开英文摘要原文

Immunotherapy has transformed the landscape of cancer treatment, with chimeric antigen receptor (CAR)-engineered T (CAR-T) cell therapy emerging as a front runner in addressing some hematological malignancies. Despite its considerable efficacy, the occurrence of severe adverse effects associated with CAR-T cell therapy has limited their scope and prompted the exploration of alternative therapeutic strategies. Natural killer (NK) cells, characterized by both their innate cytotoxicity and ability to lyse target cells without the constraint of peptide specificity conferred by a major histocompatibility complex (MHC), have similarly garnered attention as a viable immunotherapy.

As such, another therapeutic approach has recently emerged that seeks to combine the continued success of CAR-T cell therapy with the flexibility of NK cells. Clinical trials involving CAR-engineered NK (CAR-NK) cell therapy have exhibited promising efficacy with fewer deleterious side effects.

This review aims to provide a concise overview of the cellular and molecular basis of NK cell biology, facilitating a better understanding of advancements in CAR design and manufacturing. The focus is on current approaches and strategies employed in CAR-NK cell development, exploring at both preclinical and clinical settings.

We will reflect upon the achievements, advantages, and challenges intrinsic to CAR-NK cell therapy. Anticipating the maturation of CAR-NK cell therapy technology, we foresee its encouraging prospects for a broader range of cancer patients and other conditions. It is our belief that this CAR-NK progress will bring us closer to making significant strides in the treatment of refractory and recurrent cancers, as well as other immune-mediated disorders.

论文信息

作者
Yao P、Liu YG、Huang G、Hao L、Wang R
第一作者单位
Department of Health Management, Shengjing Hospital of China Medical University, Shenyang, 110004, Liaoning, China.China
通讯作者单位
Department of Pediatrics, Shengjing Hospital of China Medical University, No.36, Sanhao Street, Shenyang, 110004, Liaoning, China. shengjing_wrn@163.com.China
文献类型
综述
期刊
Experimental hematology & oncology2024 Dec 4
原文标识
PubMed 39633491 · DOI 10.1186/s40164-024-00583-7