REVIEW article

Front. Immunol.

Sec. NK and Innate Lymphoid Cell Biology

Volume 16 - 2025 | doi: 10.3389/fimmu.2025.1600411

This article is part of the Research TopicNovel Chimeric Antigen Receptor (CAR) Designs in engineering NK cells for CancerView all 3 articles

Application and Prospects of Genetic Engineering in CAR-NK Cell Therapy

Provisionally accepted
Caidong  HuCaidong Hu1Wenhong  LaiWenhong Lai2Bin  TianBin Tian3Xi  XuXi Xu2Shuiling  XieShuiling Xie2Wenting  ZhongWenting Zhong2Huiqiang  KangHuiqiang Kang2Xiaoyun  ChenXiaoyun Chen2Hailiang  LiHailiang Li2Liping  LiuLiping Liu2*
  • 1Fujian Medical University, Fuzhou, China
  • 2Department of Hematology, The First Affiliated Hospital of Gannan Medical University, Ganzhou, China
  • 3Dongying Hospital of Traditional Chinese Medicine, Dongying, China

The final, formatted version of the article will be published soon.

With the rapid advancement of genetic engineering technologies, CAR-NK cell therapy, as an emerging immunotherapeutic approach, has demonstrated significant potential.(CARs). Genetic engineering techniques have enhanced the targeting and anti-tumor activity of CAR-NK cells by optimizing key components of the CAR structure, such as signal peptides, single-chain variable fragments (scFvs), linkers, and hinge regions.Additionally, NK cells can be derived from diverse sources, including peripheral blood, umbilical cord blood, stem cells, and NK cell lines, each with its unique advantages and limitations. Although CAR-NK cell therapy has shown promising anti-tumor efficacy in preclinical studies, it still faces numerous challenges. In the future, further optimization of CAR-NK cell design through genetic engineering and overcoming the immunosuppressive tumor microenvironment will be crucial for enhancing its clinical application efficacy. This review will comprehensively discuss the current applications, technical challenges, and future directions of genetic engineering in CAR-NK cell therapy.

Keywords: Natural Killer cells, CAR-NK cells, Genetic Engineering, NK cell expansion, vectors for CAR Expression, Tumor Microenvironment

Received: 26 Mar 2025; Accepted: 05 May 2025.

Copyright: © 2025 Hu, Lai, Tian, Xu, Xie, Zhong, Kang, Chen, Li and Liu. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Liping Liu, Department of Hematology, The First Affiliated Hospital of Gannan Medical University, Ganzhou, China

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