生物材料增效NK细胞免疫疗法研究进展

Research progress in leveraging biomaterials for enhancing NK cell immunotherapy

NK细胞免疫疗法是继T细胞免疫疗法后另一种具有巨大临床前景的抗肿瘤方法。继基因工程之后,利用生物材料对NK细胞进行工程化改造也是精准、高效和低成本地构造完美人工免疫细胞的有效策略。首先,发展NK细胞表面修饰策略:通过脂质材料疏水效应、膜蛋白“受体-配体”之间非共价作用、膜蛋白的氨基酸残基共价结合、点击反应、静电相互作用等生物材料策略对NK细胞表面进行工程化修饰;其次,发展NK细胞内部修饰策略:通过纳米技术丰富NK细胞功能和NK细胞膜材料构建NK细胞仿生系统。另外,基于生物材料的技术策略被发展用于实体瘤内NK细胞原位激活:利用生物材料调控原位NK细胞在实体瘤部位的招募、识别和杀伤等功能,保障瘤内NK细胞活性,极大地改善NK细胞免疫疗法的治疗效果。本文重点综述基于生物材料增效NK细胞免疫疗法的相关研究进展。

NK cell immunotherapy is a promising antitumor therapeutic modality after the development of T cell immunotherapy.Structural modification of NK cells with biomaterials may provide a precise,efficient,and low-cost strategy to enhance NK cell immunotherapy.The biomaterial modification of NK cells can be divided into two strategies:surface engineering with biomaterials and intracellular modification.The surface engineering strategies include hydrophobic interaction of lipids,receptor-ligand interaction between membrane proteins,covalent binding to amino acid residues,click reaction and electrostatic interaction.The intracellular modification strategies are based on manipulation by nanotechnology using membranous materials from various sources of NK cells(such as exosome,vesicle and cytomembranes).Finally,the biomaterials-based strategies regulate the recruitment,recognition and cytotoxicity of NK cells in the solid tumor site in situ to boost the activity of NK cells in the tumor.This article reviews the recent research progress in enhancing NK cell therapy based on biomaterial modification,to provide a reference for further researches on engineering NK cell therapy with biomaterials.