REVIEW article

Front. Immunol.

Sec. NK and Innate Lymphoid Cell Biology

Volume 16 - 2025 | doi: 10.3389/fimmu.2025.1550652

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

Novel Strategies to Overcome Tumor Immunotherapy Resistance using ‎CAR NK cells

Provisionally accepted
Jun-Hui GuoJun-Hui Guo1Ali AfzalAli Afzal2Sadia AhmadSadia Ahmad3Ghazala SaeedGhazala Saeed3Amna RehmanAmna Rehman3Umair Ali Khan SaddozaiUmair Ali Khan Saddozai2Lei LiuLei Liu4Shihao GuoShihao Guo5*Xin-Ying JiXin-Ying Ji6*Muhammad Babar KhawarMuhammad Babar Khawar7*
  • 1First Affiliated Hospital of Henan University of Traditional Chinese Medicine, Zhengzhou, Henan Province, China
  • 2Yangzhou University, Yangzhou, Jiangsu Province, China
  • 3University of the Punjab, Lahore, Punjab, Pakistan
  • 4Second Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan Province, China
  • 5Department of Cardiology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan Province, China
  • 6Zhengzhou Shuqing Medical College, Zhengzhou, Henan Province, China
  • 7Institute of Translational Medicine, Medical College, Yangzhou University, Yangzhou, Jiangsu, 225001, PR China, Yangzhou, Jiangsu Province, China

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While immunotherapy faces obstacles, the emergence of chimeric antigen receptor (CAR) ‎engineered natural killer (NK) cells is paving new ways and might become a preferred option ‎over CAR T cells very soon. CAR NK introduce diverse cytotoxic mechanisms offering novel ‎strategies to combat tumor immunotherapy resistance. Concurrently, improvements in NK cell ‎homing and gene-edited CAR NK cell therapy offer promising avenues for overcoming ‎challenges in cancer immunotherapy. Our review addresses resistance mechanisms and ‎engineering strategies to enhance CAR NK cell functionality by improving NK cell homing ‎and migration to tumor sites, emphasizing insights from preclinical and clinical studies.‎

Keywords: CAR NK cells, Immunotherapy resistance, Tumor Microenvironment, NK cell homing, Cancer immnuotherapy

Received: 23 Dec 2024; Accepted: 02 May 2025.

Copyright: © 2025 Guo, Afzal, Ahmad, Saeed, Rehman, Saddozai, Liu, Guo, Ji and Khawar. 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:
Shihao Guo, Department of Cardiology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 96299, Henan Province, China
Xin-Ying Ji, Zhengzhou Shuqing Medical College, Zhengzhou, Henan Province, China
Muhammad Babar Khawar, Institute of Translational Medicine, Medical College, Yangzhou University, Yangzhou, Jiangsu, 225001, PR China, Yangzhou, Jiangsu Province, China

Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.

Supplementary Material