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实体瘤的精准狙击:CAR-NK细胞疗法。

Precision sniper for solid tumors: CAR-NK cell therapy.

作者信息

Li Sisi, Jing Jiajie, Chen Yueming, Chi Enjie, Wang Bingyan, Xie Ziwen, Yang Wenya, Shen Hongqiang, Pan Jianping

机构信息

Department of Clinical Medicine, Hangzhou City University School of Medicine, 51 Huzhou Street, Hangzhou, 310015, People's Republic of China.

Institute of Translational Medicine, Hangzhou City University, 51 Huzhou Street, Hangzhou, 310015, People's Republic of China.

出版信息

Cancer Immunol Immunother. 2025 Jul 24;74(9):275. doi: 10.1007/s00262-025-04106-z.

DOI:10.1007/s00262-025-04106-z
PMID:40705122
Abstract

Chimeric antigen receptor (CAR) represents a novel targeted therapy that uses genetic engineering to modify effector cells for precise tumor cell targeting. Chimeric antigen receptor-T (CAR-T) cell immunotherapy, which employs T cells as effectors, has demonstrated significant efficacy in treating hematologic malignancies. However, its efficacy against solid tumors remains inadequate and is accompanied by toxic side effects, including cytokine release syndrome, neurotoxicity and on-target/off-tumor effects. In contrast to T cells, natural killer (NK) cells exhibit a broader source range and can non-specifically lyse tumor cells. Moreover, it can also reduce toxicity and side effects to some extent. This review comprehensively examines recent research progress on CAR-NK therapy for solid tumors, encompassing both in vivo and in vitro studies, with a focus on CAR-NK cell design and production methods. Drawing upon laboratory and clinical evidence, this review summarizes the current challenges and side effects associated with CAR-NK technology.

摘要

嵌合抗原受体(CAR)代表了一种新型的靶向治疗方法,它利用基因工程改造效应细胞,以精确靶向肿瘤细胞。以T细胞作为效应细胞的嵌合抗原受体T(CAR-T)细胞免疫疗法在治疗血液系统恶性肿瘤方面已显示出显著疗效。然而,其对实体瘤的疗效仍然不足,并且伴有毒性副作用,包括细胞因子释放综合征、神经毒性和靶向脱瘤效应。与T细胞不同,自然杀伤(NK)细胞来源范围更广,能够非特异性地裂解肿瘤细胞。此外,它还能在一定程度上降低毒性和副作用。本综述全面考察了CAR-NK疗法治疗实体瘤的最新研究进展,涵盖体内和体外研究,重点关注CAR-NK细胞的设计和生产方法。基于实验室和临床证据,本综述总结了与CAR-NK技术相关的当前挑战和副作用。

相似文献

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Precision sniper for solid tumors: CAR-NK cell therapy.实体瘤的精准狙击:CAR-NK细胞疗法。
Cancer Immunol Immunother. 2025 Jul 24;74(9):275. doi: 10.1007/s00262-025-04106-z.
2
CAR-NK, a Splendid Strategy for Cancer, Especially for Gynecologic Tumor.嵌合抗原受体自然杀伤细胞疗法(CAR-NK),一种治疗癌症的卓越策略,尤其适用于妇科肿瘤。
Immun Inflamm Dis. 2025 Jun;13(6):e70210. doi: 10.1002/iid3.70210.
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Constitutive IL-7 signaling promotes CAR-NK cell survival in the solid tumor microenvironment but impairs tumor control.组成性白细胞介素-7信号通路促进实体瘤微环境中嵌合抗原受体自然杀伤(CAR-NK)细胞的存活,但损害肿瘤控制。
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本文引用的文献

1
CD147-CAR-NK cell therapy shows minimal toxicities in human CD147 transgenic mouse model with solid tumors.CD147嵌合抗原受体自然杀伤细胞(CD147-CAR-NK)疗法在携带实体瘤的人CD147转基因小鼠模型中显示出极低的毒性。
Mol Ther Oncol. 2025 Feb 26;33(1):200957. doi: 10.1016/j.omton.2025.200957. eCollection 2025 Mar 20.
2
Emerging combined CAR-NK cell therapies in cancer treatment: Finding a dancing partner.癌症治疗中新兴的联合CAR-NK细胞疗法:寻找舞伴。
Mol Ther. 2025 Jan 3. doi: 10.1016/j.ymthe.2024.12.057.
3
[Retracted] Upregulation of estrogen receptor mediates migration, invasion and proliferation of endometrial carcinoma cells by regulating the PI3K/AKT/mTOR pathway.
[已撤回] 雌激素受体上调通过调节PI3K/AKT/mTOR通路介导子宫内膜癌细胞的迁移、侵袭和增殖。
Oncol Rep. 2025 Feb;53(2). doi: 10.3892/or.2024.8856. Epub 2024 Dec 20.
4
Hyper-Interferon Sensitive Influenza Induces Adaptive Immune Responses and Overcomes Resistance to Anti-PD-1 in Murine Non-Small Cell Lung Cancer.高干扰素敏感性流感病毒在小鼠非小细胞肺癌中诱导适应性免疫反应并克服对抗程序性死亡蛋白1(anti-PD-1)的耐药性。
Cancer Immunol Res. 2024 Dec 3;12(12):1765-1779. doi: 10.1158/2326-6066.CIR-23-1075.
5
Acute T-cell lymphoblastic leukemia: chimeric antigen receptor technology may offer a new hope.急性 T 细胞淋巴细胞白血病:嵌合抗原受体技术可能带来新希望。
Front Immunol. 2024 Aug 13;15:1410519. doi: 10.3389/fimmu.2024.1410519. eCollection 2024.
6
Current Strategies to Improve Chimeric Antigen Receptor T (CAR-T) Cell Persistence.改善嵌合抗原受体T(CAR-T)细胞持久性的当前策略。
Cureus. 2024 Jul 24;16(7):e65291. doi: 10.7759/cureus.65291. eCollection 2024 Jul.
7
Specific multivalent molecules boost CRISPR-mediated transcriptional activation.特定的多价分子可增强 CRISPR 介导的转录激活。
Nat Commun. 2024 Aug 22;15(1):7222. doi: 10.1038/s41467-024-51694-y.
8
Engineered CAR-NK Cells with Tolerance to H2O2 and Hypoxia Can Suppress Postoperative Relapse of Triple-Negative Breast Cancers.工程化 CAR-NK 细胞对 H2O2 和缺氧的耐受性可抑制三阴性乳腺癌术后复发。
Cancer Immunol Res. 2024 Nov 4;12(11):1574-1588. doi: 10.1158/2326-6066.CIR-23-1017.
9
Emerging roles of CAR-NK cell therapies in tumor immunotherapy: current status and future directions.嵌合抗原受体自然杀伤细胞(CAR-NK)疗法在肿瘤免疫治疗中的新兴作用:现状与未来方向。
Cell Death Discov. 2024 Jul 10;10(1):318. doi: 10.1038/s41420-024-02077-1.
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Disruption of TGF-β signaling pathway is required to mediate effective killing of hepatocellular carcinoma by human iPSC-derived NK cells.阻断 TGF-β 信号通路是人类诱导多能干细胞来源的 NK 细胞有效杀伤肝癌细胞所必需的。
Cell Stem Cell. 2024 Sep 5;31(9):1327-1343.e5. doi: 10.1016/j.stem.2024.06.009. Epub 2024 Jul 9.