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Glycoengineering of Natural Killer Cells with CD22 Ligands for Enhanced Anticancer Immunotherapy
ACS Central Science ( IF 18.2 ) Pub Date : 2020-03-05 , DOI: 10.1021/acscentsci.9b00956
Xianwu Wang 1 , Shuyao Lang 2 , Yunpeng Tian 3 , Jianghong Zhang 3 , Xu Yan 4 , Zhihong Fang 5 , Jian Weng 1 , Na Lu 6 , Xuanjun Wu 2, 6 , Tianlu Li 2, 6 , Hongzhi Cao 6 , Zhu Li 3 , Xuefei Huang 2
Affiliation  

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.

中文翻译:

CD22配体的天然杀伤细胞的糖工程增强抗癌免疫治疗。

免疫细胞的过继转移正积极地用于癌症治疗。天然杀伤(NK)细胞是一类细胞毒性免疫细胞,通常缺乏对癌症的固有选择性。为了赋予肿瘤靶向能力并增强抗癌效果,糖工程NK细胞建立了一种新的策略。CD22的基于碳水化合物的配体(B细胞淋巴瘤的标志物)通过代谢工程或糖聚合物插入而引入NK细胞。这样的NK细胞以CD22依赖性方式对CD22 +淋巴瘤细胞表现出大大增强的细胞毒性。重要的是,CD22 +工程化的NK细胞可有效杀死人类癌症患者的淋巴瘤细胞系和原发性淋巴瘤细胞。此外,糖工程化的NK细胞为荷瘤小鼠提供了重要的保护。因此,NK细胞糖工程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。
更新日期:2020-03-26
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