Ryu Minseon, Kim Eunha, Kim Sungjun, Kim Kyobum
Department of Chemical & Biochemical Engineering, Dongguk University, Seoul, 04620, Republic of Korea.
Mater Today Bio. 2025 Jun 9;33:101965. doi: 10.1016/j.mtbio.2025.101965. eCollection 2025 Aug.
Natural killer (NK) cells are proving a powerful platform in cancer immunotherapy due to their innate cytotoxicity and ability to recognize tumor cells independently of antigen presentation. In preclinical and clinical studies, engineered NK cells expressing chimeric antigen receptors (CARs) have demonstrated strong antitumor efficacy, showcasing the potential of genetic reprogramming to enhance specificity and activation. In parallel, biomaterial-assisted surface engineering has gained momentum as a complementary strategy, offering a genome-independent and modular means of customizing NK cell functionality. Recent advances in covalent conjugation, metabolic glycoengineering, bio-orthogonal click chemistry, and hydrophobic insertion using biomaterials have facilitated the precise presentation of targeting ligands and immunomodulatory molecules directly onto the NK cell membrane. These strategies support programmable cell-tumor interactions, while maintaining the native cytotoxicity of NK cells. Although several challenges remain, including persistence and control of effector responses, surface engineering approaches offer practical advantages in flexibility, reversibility, and manufacturing. This review highlights key advances in NK cell-based cancer immunotherapy, with particular focus on: (1) the therapeutic potential and clinical application of native NK cells, (2) the development of CAR-NK cell platforms, and (3) emerging biomaterial-assisted surface engineering strategies to enhance immune synapse. Together, these developments expand the toolkit for NK cell-based therapies and suggest that material-guided engineering may play a valuable role alongside genetic strategies in shaping the next generation of cancer immunotherapy.
自然杀伤（NK）细胞因其固有的细胞毒性以及独立于抗原呈递识别肿瘤细胞的能力，正成为癌症免疫治疗中一个强大的平台。在临床前和临床研究中，表达嵌合抗原受体（CAR）的工程化NK细胞已显示出强大的抗肿瘤功效，展现了基因重编程在增强特异性和激活方面的潜力。与此同时，生物材料辅助的表面工程作为一种补充策略已得到发展，提供了一种独立于基因组且模块化的定制NK细胞功能的方法。利用生物材料进行共价偶联、代谢糖工程、生物正交点击化学和疏水插入等方面的最新进展，已促进了靶向配体和免疫调节分子直接在NK细胞膜上的精确呈现。这些策略支持可编程的细胞 - 肿瘤相互作用，同时保持NK细胞的天然细胞毒性。尽管仍存在一些挑战，包括效应器反应的持久性和控制，但表面工程方法在灵活性、可逆性和制造方面具有实际优势。本综述重点介绍了基于NK细胞的癌症免疫治疗的关键进展，特别关注：（1）天然NK细胞的治疗潜力和临床应用，（2）CAR - NK细胞平台的发展，以及（3）新兴的生物材料辅助表面工程策略以增强免疫突触。总之，这些进展扩展了基于NK细胞疗法的工具集，并表明材料引导的工程在塑造下一代癌症免疫治疗方面可能与基因策略一起发挥重要作用。
