Marr Bryan, Jo Donghyeon, Jang Mihue, Lee Seung-Hwan
Department of Biochemistry, Microbiology and Immunology, Faculty of Medicine, University of Ottawa, Ottawa, ON K1H 8M5, Canada.
Medicinal Materials Research Center, Biomedical Research Division, Korea Institute of Science and Technology, Seoul 02792, Korea.
Immune Netw. 2025 Apr 9;25(2):e17. doi: 10.4110/in.2025.25.e17. eCollection 2025 Apr.
NK cell adoptive cell therapy (ACT) has emerged as a promising strategy for cancer immunotherapy, offering advantages in scalability, accessibility, efficacy, and safety. 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.
自然杀伤（NK）细胞过继性细胞疗法（ACT）已成为一种很有前景的癌症免疫治疗策略，在可扩展性、可及性、疗效和安全性方面具有优势。包含饲养细胞和细胞因子鸡尾酒的激活和扩增方案，已能够生产出临床相关数量的高功能NK细胞。NK细胞工程的进展，包括CRISPR介导的基因编辑和嵌合抗原受体技术，进一步增强了细胞毒性、持久性和肿瘤靶向性。过继转移后的细胞因子支持，特别是使用白细胞介素-2（IL-2）和白细胞介素-15（IL-15），对于促进NK细胞存活、增殖和抗肿瘤活性仍然至关重要，尽管存在诸如调节性T细胞扩增和细胞因子相关毒性等持续挑战。本综述探讨了IL-2和IL-15在基于NK细胞的ACT中的不断演变的作用，评估它们的潜力和局限性，并强调优化这些细胞因子以实现有效癌症免疫治疗的策略。
