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CAR-T 细胞与 CAR-NK 细胞的结构、遗传与临床比较:伙伴还是竞争者?

英文原题:A structural, genetic and clinical comparison of CAR-T cells and CAR-NK cells: companions or competitors?

PubMed 2024/10/04(内容时间) Front Immunol Q1 · IF 7(JCR 2025)

研究概要

近年来,随着嵌合抗原受体(CAR)T 细胞疗法在血液系统肿瘤中取得突破性进展,以及细胞工程技术的进步,对其他免疫细胞的探索受到了广泛关注。

中文摘要

近年来,嵌合抗原受体(CAR)T 细胞治疗在血液系统癌症中取得突破,细胞工程技术也不断进步,促使研究者广泛探索其他免疫细胞。CAR 疗法已从 T 细胞拓展至 CAR 自然杀伤(NK)细胞和 CAR 巨噬细胞,这些疗法已在临床试验领域占据重要位置。CAR 黏膜相关恒定 T(MAIT)细胞等较少见的免疫细胞也开始受到关注。这一进展正在推动精准医疗,并促进现成型生物疗法的开发。鉴于 NK 细胞的独特特性,过继性 NK 细胞免疫治疗已发展为通用、异体、“现成型”治疗策略。CAR-NK 细胞具有靶向肿瘤的特异性细胞毒作用,但似乎不具备 CAR-T 细胞相关副作用。CAR-NK 细胞因此是癌症免疫治疗的潜在优良候选者。然而,其应用受到重大挑战限制,尤其是 CAR-NK 细胞在体内持久性有限,这阻碍其持续发挥抗癌作用。基于以上背景,本综述讨论 CAR-T 和 CAR-NK 细胞治疗血液系统恶性肿瘤的现状和应用,并比较这两类基因修饰免疫细胞的结构、遗传学和临床结局。

展开英文摘要原文

In recent years, following the groundbreaking achievements of chimeric antigen receptor (CAR) T cell therapy in hematological cancers, and advancements in cell engineering technologies, the exploration of other immune cells has garnered significant attention. CAR-Therapy extended beyond T cells to include CAR natural killer (NK) cells and CAR-macrophages, which are firmly established in the clinical trial landscape. Less conventional immune cells are also making their way into the scene, such as CAR mucosal-associated invariant T (MAIT) cells. This progress is advancing precision medicine and facilitating the development of ready-to-use biological treatments. However, in view of the unique features of natural killer cells, adoptive NK cell immunotherapy has emerged as a universal, allogenic, "off-the shelf" therapeutic strategy. CAR-NK cytotoxic cells present targeted tumor specificity but seem to be devoid of the side effects associated with CAR-T cells. CAR-NK cells appear to be potentially promising candidates for cancer immunotherapy. However, their application is hindered by significant challenges, particularly the limited persistence of CAR-NK cells in the body, which poses a hurdle to their sustained effectiveness in treating cancer. Based upon the foregoing, this review discusses the current status and applications of both CAR-T cells and CAR-NK cells in hematological cancers, and provides a comparative analysis of the structure, genetics, and clinical outcomes between these two types of genetically modified immune cells.

论文信息

作者
Andrea AE、Chiron A、Sarrabayrouse G、Bessoles S、Hacein-Bey-Abina S
第一作者单位
Department of Biology, Faculty of Arts and Sciences, Saint George University of Beirut, Beirut, Lebanon.
通讯作者单位
Université Paris Cité, Centre National de la Recherche Scientifique, Institut National de la Santé et de la Recherche Médicale, Unité des Technologies Chimiques et Biologiques pour la Santé (UTCBS), Paris, France.France
文献类型
综述 · 对照研究
期刊
Frontiers in immunology2024
原文标识
PubMed 39430751 · DOI 10.3389/fimmu.2024.1459818