Wang Xianwu, Lang Shuyao, Tian Yunpeng, Zhang Jianghong, Yan Xu, Fang Zhihong, Weng Jian, Lu Na, Wu Xuanjun, Li Tianlu, Cao Hongzhi, Li Zhu, Huang Xuefei
Department of Biomaterials, College of Materials, Xiamen University, 422 Siming Nan Road, Xiamen 361005, P. R. China.
Departments of Chemistry and Biomedical Engineering, Institute for Quantitative Health Science and Engineering, Michigan State University, East Lansing, Michigan 48824, United States.
ACS Cent Sci. 2020 Mar 25;6(3):382-389. doi: 10.1021/acscentsci.9b00956. Epub 2020 Mar 5.
Adoptive transfer of immune cells is being actively pursued for cancer treatment. Natural killer (NK) cells, a class of cytotoxic immune cells, generally lack inherent selectivities toward cancer. To bestow tumor-targeting abilities and enhance anticancer efficacy, a new strategy is established to glycoengineer NK cells. Carbohydrate-based ligands for CD22, a marker for B cell lymphoma, are introduced onto NK cells through either metabolic engineering or glyco-polymer insertion. Such NK cells exhibited greatly enhanced cytotoxicities toward CD22 lymphoma cells in a CD22-dependent manner. Importantly, both CD22 lymphoma cell lines and primary lymphoma cells from human cancer patients can be effectively killed by the engineered NK cells. Furthermore, glycoengineered NK cells provided significant protection to tumor-bearing mice. Thus, NK cell glycoengineering is an exciting new approach for cancer treatment complementing the current immune cell genetic engineering strategy.
免疫细胞的过继性转移正在被积极用于癌症治疗。自然杀伤（NK）细胞是一类细胞毒性免疫细胞，通常对癌症缺乏内在的选择性。为了赋予肿瘤靶向能力并提高抗癌疗效，建立了一种对NK细胞进行糖工程改造的新策略。通过代谢工程或糖聚合物插入，将用于B细胞淋巴瘤标志物CD22的基于碳水化合物的配体引入NK细胞。这种NK细胞以CD22依赖的方式对CD22淋巴瘤细胞表现出大大增强的细胞毒性。重要的是，工程化的NK细胞可以有效杀死CD22淋巴瘤细胞系以及来自人类癌症患者的原发性淋巴瘤细胞。此外，糖工程改造的NK细胞为荷瘤小鼠提供了显著的保护。因此，NK细胞糖工程改造是一种令人兴奋的癌症治疗新方法，可补充当前的免疫细胞基因工程策略。
