研究动态
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代谢性糖基标记固定树突状细胞膜并增强树突状细胞疫苗的抗肿瘤疗效。

Metabolic glycan labeling immobilizes dendritic cell membrane and enhances antitumor efficacy of dendritic cell vaccine.

发表日期:2023 Aug 19
作者: Joonsu Han, Rimsha Bhatta, Yusheng Liu, Yang Bo, Alberto Elosegui-Artola, Hua Wang
来源: CYTOKINE & GROWTH FACTOR REVIEWS

摘要:

树突状细胞(DC)疫苗是最早被美国食品与药品管理局(FDA)批准用于癌症免疫治疗的疫苗之一,但其细胞毒性T淋巴细胞(CTL)反应和治疗效果有限。本文报道了一种简便的代谢标记方法,可用于定向调节移植的DCs以开发增强的DC疫苗。我们发现,代谢糖标记能够降低DCs的膜动力性,激活DCs并改善其抗原呈递以及随后的T细胞启动功能。代谢糖标记本身能够增强DC疫苗的抗肿瘤功效。此外,通过代谢糖标记引入的细胞表面化学标记(如烯丙基基团),还可以实现细胞内生性细胞因子的共价修饰,并进一步增强CTL反应和抗肿瘤功效。我们的DC标记与靶向技术提供了一种改善DC疫苗治疗效果的策略,对临床制造过程的干预最小。 © 2023.施普林格自然出版集团有限公司。
Dendritic cell (DC) vaccine was among the first FDA-approved cancer immunotherapies, but has been limited by the modest cytotoxic T lymphocyte (CTL) response and therapeutic efficacy. Here we report a facile metabolic labeling approach that enables targeted modulation of adoptively transferred DCs for developing enhanced DC vaccines. We show that metabolic glycan labeling can reduce the membrane mobility of DCs, which activates DCs and improves the antigen presentation and subsequent T cell priming property of DCs. Metabolic glycan labeling itself can enhance the antitumor efficacy of DC vaccines. In addition, the cell-surface chemical tags (e.g., azido groups) introduced via metabolic glycan labeling also enable in vivo conjugation of cytokines onto adoptively transferred DCs, which further enhances CTL response and antitumor efficacy. Our DC labeling and targeting technology provides a strategy to improve the therapeutic efficacy of DC vaccines, with minimal interference upon the clinical manufacturing process.© 2023. Springer Nature Limited.