Annals of Laboratory Medicine

Korean Society for Laboratory Medicine (대한진단검사의학회)
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Advancing Natural Killer Cell Therapy: Genetic Engineering Strategies for Enhanced Cancer Immunotherapy

  • Joo Dong Park (Department of Integrative Biotechnology, College of Biotechnology and Bioengineering, Sungkyunkwan University) ;
  • Ha Eun Shin (Department of Tropical Medicine, Medical Microbiology and Pharmacology, John A. Burns School Medicine, University of Hawai'i at Manoa) ;
  • Yeon Su An (Department of Integrative Biotechnology, College of Biotechnology and Bioengineering, Sungkyunkwan University) ;
  • Hye Jung Jang (Department of Integrative Biotechnology, College of Biotechnology and Bioengineering, Sungkyunkwan University) ;
  • Juwon Park (Department of Tropical Medicine, Medical Microbiology and Pharmacology, John A. Burns School Medicine, University of Hawai'i at Manoa) ;
  • Se-Na Kim (Department of Industrial Cosmetic Science, Chungbuk National University) ;
  • Chun Gwon Park (Department of Biomedical Engineering, Institute for Cross-disciplinary Studies, Sungkyunkwan University) ;
  • Wooram Park (Department of Integrative Biotechnology, College of Biotechnology and Bioengineering, Sungkyunkwan University)
  • Received : 2024.07.19
  • Accepted : 2024.12.27
  • Published : 2025.03.01
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Abstract

Natural killer (NK) cells are pivotal innate immune system components that exhibit spontaneous cytolytic activity against abnormal cells, such as infected and tumor cells. NK cells have shown significant promise in adoptive cell therapy because of their favorable safety profiles and minimal toxicity in clinical settings. Despite their advantages, the therapeutic application of unmodified NK cells faces challenges, including limited in vivo persistence, particularly in the immunosuppressive tumor microenvironment. Recent advances in genetic engineering have enhanced the therapeutic potential of NK cells by addressing these limitations and improving their therapeutic efficacy. In this review, we have described various methodologies for the genetic modification of NK cells, including viral vectors, electroporation, and nanoparticle-based approaches. The ongoing research on nanomaterial-based approaches highlights their potential to overcome current limitations in NK cell therapy, paving the way for advanced cancer therapy and improved clinical outcomes. In this review, we also emphasize the potential of engineered NK cells in cancer immunotherapy and other clinical applications, highlighting the expanding scope of NK cell-based treatments and the critical role of innovative genetic engineering techniques.

Keywords

Acknowledgement

This work was supported by Basic Science Research Program grants (RS-2024-00350878, RS-2023-00218648, and RS-2023-00242443) through the National Research Foundation of Korea (NRF) grants, the KIST Institutional Program (2E32351-23-130), and Regional Innovation Strategy (RIS) through the NRF funded by the Ministry of Education (MOE) (2021RIS-001).

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