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嵌合抗原受体(CAR)-NK 细胞疗法在胃肠道(GI)肿瘤中的应用:一个新领域

英文原题:Chimeric antigen receptor (CAR)-NK cell therapy in gastrointestinal (GI) cancers; a new arena.

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Chimeric antigen receptor (CAR)-NK cell therapy in gastrointestinal (GI) cancers; a new arena.

PubMed 2025/07/19(内容时间) Exp Cell Res Q2 · IF 3.5(JCR 2025)

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中文摘要

肿瘤微环境(TME)高度复杂,免疫逃逸是恶性肿瘤促进肿瘤发展和扩散的关键特征。研究表明,T细胞免疫治疗取得的有限成功凸显了其他先进免疫疗法日益增长的重要性,特别是基于自然杀伤(NK)细胞的疗法。人类NK细胞是抗击恶性肿瘤的主要先天免疫细胞,在胃肠道(GI)癌症的TME中表现出显著的多样性。目前,针对GI癌症免疫治疗,嵌合抗原受体(CAR)工程化NK细胞的进展日益受到关注。CAR-NK细胞相较于CAR-T 细胞的优势包括安全性增强,细胞因子释放综合征(CRS)和移植物抗宿主病(GVHD)的发生极少或没有。

此外,CAR-NK细胞采用多种方法刺激细胞毒性功能,并且非常适合“现货型”制造。这些效应细胞可以通过基因改造特异性识别不同抗原,增强其在体内增殖和存活的能力,提高其进入GI癌症并克服肿瘤微环境中耐药性的能力。这最终导致所需的抗肿瘤反应。

值得注意的是,CAR-NK细胞作为肿瘤相关抗原(TAAs)的抗原受体,有效重定向NK细胞并促进肿瘤相关免疫监视。本研究探讨了CAR-NK细胞在治疗GI癌症方面的治疗能力进展。

展开英文摘要原文

Tumor microenvironment (TME) is highly complex, and immune escape is a crucial characteristic of malignancies that promotes tumor development and spread. According to studies, the limited success achieved by T cell immunotherapy highlights the growing importance of other advanced immunotherapies, specifically those based on natural killer (NK) cells.

Human NK cells are the primary innate immune cells that combat malignancies and exhibit significant diversity within the TME of gastrointestinal (GI) cancers. There is currently a growing interest in the advancement of chimeric antigen receptor (CAR)-engineered NK cells for GI cancer immunotherapy. The advantages of CAR-NK cells over CAR-T cells include enhanced safety, with minimal or no occurrence of cytokine release syndrome (CRS) and graft-versus-host disease (GVHD).

Additionally, CAR-NK cells employ many methods to stimulate cytotoxic function and are very feasible for "off-the-shelf" manufacture. These effector cells can be genetically altered to specifically recognize different antigens, enhance their ability to multiply and survive in the body, increase their ability to enter GI cancers and overcome resistance in the tumor microenvironment.

This ultimately leads to a desired anti-tumor response. Significantly, CAR-NK cells serve as antigen receptors for tumor-associated antigens (TAAs), effectively diverting NK cells and promoting tumor-related immunosurveillance.

This study examines the advancements in the therapeutic capabilities of CAR-NK cells for treating GI cancers.

论文信息

作者
Alkhathami AG、Ahmed AT、Hussn A、RenukaJyothi S、Panigrahi R、Al-Hetty HRAK、Negi H、Jassal P
第一作者单位
Department of Clinical Laboratory Sciences, College of Applied Medical Sciences, King Khalid University, Abha, Saudi Arabia.Saudi Arabia
通讯作者单位
Department of Biology, College of Education for Pure Sciences, University of Anbar, Ramadi, 31001, Anbar, Iraq. Electronic address: hussin.riyadh@uoanbar.edu.iq.Saudi Arabia
文献类型
综述
期刊
Experimental cell research2025 Jul 15
原文标识
PubMed 40692031 · DOI 10.1016/j.yexcr.2025.114683