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Cytokines in Focus: IL-2 and IL-15 in NK Adoptive Cell Cancer Immunotherapy

  • Bryan Marr (Department of Biochemistry, Microbiology and Immunology, Faculty of Medicine, University of Ottawa) ;
  • Donghyeon Jo (Department of Biochemistry, Microbiology and Immunology, Faculty of Medicine, University of Ottawa) ;
  • Mihue Jang (Medicinal Materials Research Center, Biomedical Research Division, Korea Institute of Science and Technology) ;
  • Seung-Hwan Lee (Department of Biochemistry, Microbiology and Immunology, Faculty of Medicine, University of Ottawa)
  • Received : 2025.01.21
  • Accepted : 2025.03.06
  • Published : 2025.04.30
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Abstract

NK cell adoptive cell therapy (ACT) has emerged as a promising strategy for cancer immunotherapy, offering advantages in scalability, accessibility, efficacy, and safety. Ex vivo activation and expansion protocols, incorporating feeder cells and cytokine cocktails, have enabled the production of highly functional NK cells in clinically relevant quantities. Advances in NK cell engineering, including CRISPR-mediated gene editing and chimeric Ag receptor technologies, have further enhanced cytotoxicity, persistence, and tumor targeting. Cytokine support post-adoptive transfer, particularly with IL-2 and IL-15, remains critical for promoting NK cell survival, proliferation, and anti-tumor activity despite persistent challenges such as regulatory T cell expansion and cytokine-related toxicities. This review explores the evolving roles of IL-2 and IL-15 in NK cell-based ACT, evaluating their potential and limitations, and highlights strategies to optimize these cytokines for effective cancer immunotherapy.

Keywords

Acknowledgement

This work was supported by the National Research Foundation of Korea Grant funded by the Korean Government (grant numbers: 2RS-2024-00509114) and the Canadian Institutes of Health Research (PJT-178197 & PJT-195765).

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