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突破壁垒:嵌合抗原受体自然杀伤细胞(CAR-NK)疗法在女性相关癌症中的突破

Breaking barriers: CAR-NK cell therapy breakthroughs in female-related cancers.

作者信息

Ahmad Ghorbani Vanan, Nouri Samaneh, Mohammad Gholian Amirhossein, Abdollahi Eileen, Ghorbaninezhad Farid, Tahmasebi Safa, Eterafi Majid, Askari Mohammad Reza, Safarzadeh Elham

机构信息

Student Research Committee, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran; Cancer Immunology and Immunotherapy Research Center, Ardabil University of Medical Sciences, Ardabil, Iran.

Cancer Immunology and Immunotherapy Research Center, Ardabil University of Medical Sciences, Ardabil, Iran.

出版信息

Biomed Pharmacother. 2025 Jun;187:118071. doi: 10.1016/j.biopha.2025.118071. Epub 2025 Apr 19.


DOI:10.1016/j.biopha.2025.118071
PMID:40253831
Abstract

Cancer stands as a leading cause of mortality globally. The main female-related malignancies are breast cancer, with 2.3 million new cases annually, and ovarian cancer, with 300,000 new cases per year worldwide. The current treatments like surgery, chemotherapy, and radiation therapy have presumably had deficiencies in sustaining long-term anti-tumor responses. Cellular immunotherapy, also referred to as adoptive cell therapy, has shown encouraging advances by employing genetically modified immune cells in fighting cancer by engineering chimeric antigen receptors (CARs) mainly on T cells and natural killer (NK) cells. Studies in NK cell therapies involve unmodified NK cells and CAR-NK cell therapies, targeting cancer cells while limiting the destruction of normal cells. CAR-NK cells represent the next generation of therapeutic immune cells that have been shown to eliminate malignancies through CAR-dependent and CAR-independent mechanisms. They also represent possible candidates for "off-the-shelf" therapies due to their advantages, including the ability to target cancer cells independently of the major histocompatibility complex, reduced risk of alloreactivity, and fewer severe toxicities compared to CAR-T cells. To date, there have been no comprehensive review studies examining the therapeutic potential of CAR-NK cell therapy specifically for female-related malignancies, such as breast and ovarian cancers. This review offers a thorough exploration of CAR-NK cell therapy in relation to these cancers and their responses to treatment.

摘要

癌症是全球主要的死亡原因之一。与女性相关的主要恶性肿瘤是乳腺癌,全球每年有230万新发病例,以及卵巢癌,每年有30万新发病例。目前的治疗方法,如手术、化疗和放疗,在维持长期抗肿瘤反应方面可能存在不足。细胞免疫疗法,也称为过继性细胞疗法,通过在主要在T细胞和自然杀伤(NK)细胞上构建嵌合抗原受体(CAR)来利用基因改造的免疫细胞对抗癌症,已显示出令人鼓舞的进展。NK细胞疗法的研究包括未修饰的NK细胞和CAR-NK细胞疗法,旨在靶向癌细胞同时限制对正常细胞的破坏。CAR-NK细胞代表了下一代治疗性免疫细胞,已证明它们可通过CAR依赖性和CAR非依赖性机制消除恶性肿瘤。由于其优势,包括能够独立于主要组织相容性复合体靶向癌细胞、降低同种异体反应性风险以及与CAR-T细胞相比严重毒性更少,它们也代表了“现成”疗法的可能候选者。迄今为止,尚未有全面的综述研究专门探讨CAR-NK细胞疗法对乳腺癌和卵巢癌等与女性相关的恶性肿瘤的治疗潜力。本综述对CAR-NK细胞疗法与这些癌症及其治疗反应进行了全面探讨。

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