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.

树突状细胞 (DC) 疫苗是 FDA 首批批准的癌症免疫疗法之一，但受到细胞毒性 T 淋巴细胞 (CTL) 反应和治疗效果有限的限制。在这里，我们报告了一种简便的代谢标记方法，该方法能够对过继转移的 DC 进行有针对性的调节，以开发增强型 DC 疫苗。我们发现代谢聚糖标记可以降低 DC 的膜迁移率，从而激活 DC 并改善 DC 的抗原呈递和随后的 T 细胞启动特性。代谢聚糖标记本身可以增强DC疫苗的抗肿瘤功效。此外，通过代谢聚糖标记引入的细胞表面化学标签（例如叠氮基）还能够在体内将细胞因子缀合到过继转移的DC上，这进一步增强了CTL反应和抗肿瘤功效。我们的 DC 标记和靶向技术提供了一种提高 DC 疫苗治疗效果的策略，同时对临床生产过程的干扰最小。