Cao Yisen, Wang Liying, Wang Liang
Fujian Medical University.
Laboratory of Gynecologic Oncology, Fujian Maternity and Child Health Hospital, College of Clinical Medicine for Obstetrics & Gynecology and Pediatrics, Fujian Medical University, Fuzhou, Fujian, China.
Immun Inflamm Dis. 2025 Jun;13(6):e70210. doi: 10.1002/iid3.70210.
BACKGROUND: NK cells are a class of innate lymphocytes capable of nonspecifically killing tumor cells without MHC restriction or prior sensitization. Recent advancements in biotechnology, particularly the development of chimeric antigen receptors (CAR) and related technologies, have enabled targeted tumor cell elimination. CAR endows NK cells with enhanced functionality, with the extracellular domains typically consisting of single-chain variable fragments (scFv) for targeting specific antigens. CAR-NK cells have shown excellent results in several preclinical studies and clinical trials for hematologic malignancies. However, their clinical application in the treatment of solid tumors is still insufficient. Current treatments for gynecological cancers primarily involve surgery, chemotherapy, and radiotherapy, all of which often present substantial side effects and variable efficacy. While CAR-T cell therapy has shown effectiveness in certain gynecological tumors, its clinical application is hindered by severe side effects, such as Cytokine Release Syndrome (CRS) and Graft-Versus-Host Disease (GVHD). CAR-NK cell therapy offers improved safety profiles in clinical applications. OBJECTIVE: This review aims to systematically evaluate recent methodological innovations in CAR-NK engineering and their translational potential in tumor-targeted treatment, providing valuable insights for clinical trials and studies. METHODS: Electronic databases, including PubMed and Web of Science were searched for relevant literature. Keywords are as follows: CAR-NK cell; Chimeric antigen receptor; Solid tumor; cell therapy; gynecological cancers. RESULTS: CAR-NK engineering has innovations such as multi-targeted CAR design, gene editing for enhanced persistence, and "off-the-shelf" CAR-NK cells compared to CAR-T cells. CONCLUSION: CAR-NK cell therapy combines safety and anti-tumor efficacy, particularly for gynecological cancers.
背景:自然杀伤(NK)细胞是一类先天性淋巴细胞,能够在无主要组织相容性复合体(MHC)限制或无需预先致敏的情况下非特异性杀伤肿瘤细胞。生物技术的最新进展,特别是嵌合抗原受体(CAR)及相关技术的发展,使得靶向性肿瘤细胞清除成为可能。CAR赋予NK细胞增强的功能,其细胞外结构域通常由用于靶向特定抗原的单链可变片段(scFv)组成。CAR-NK细胞在血液系统恶性肿瘤的多项临床前研究和临床试验中已显示出优异的效果。然而,它们在实体瘤治疗中的临床应用仍不足。目前妇科癌症的治疗主要包括手术、化疗和放疗,所有这些治疗方法往往都有严重的副作用且疗效不一。虽然CAR-T细胞疗法在某些妇科肿瘤中已显示出有效性,但其临床应用受到严重副作用的阻碍,如细胞因子释放综合征(CRS)和移植物抗宿主病(GVHD)。CAR-NK细胞疗法在临床应用中具有更好的安全性。 目的:本综述旨在系统评估CAR-NK工程的最新方法创新及其在肿瘤靶向治疗中的转化潜力,为临床试验和研究提供有价值的见解。 方法:检索包括PubMed和Web of Science在内的电子数据库以获取相关文献。关键词如下:CAR-NK细胞;嵌合抗原受体;实体瘤;细胞疗法;妇科癌症。 结果:与CAR-T细胞相比,CAR-NK工程具有多靶点CAR设计、用于增强持久性的基因编辑以及“现货”CAR-NK细胞等创新。 结论:CAR-NK细胞疗法兼具安全性和抗肿瘤疗效,尤其适用于妇科癌症。
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