Department of Materials Science and Engineering, University of Illinois at Urbana-Champaign, Urbana, IL, 61801, USA.
Cell and Tissue Mechanobiology Laboratory, Francis Crick Institute, London, UK.
Nat Commun. 2023 Aug 19;14(1):5049. doi: 10.1038/s41467-023-40886-7.
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) 疫苗是首批获得美国食品药品监督管理局 (FDA) 批准的癌症免疫疗法之一，但由于细胞毒性 T 淋巴细胞 (CTL) 反应和治疗效果有限而受到限制。在这里，我们报告了一种简便的代谢标记方法，可用于靶向调节过继转移的 DC，以开发增强的 DC 疫苗。我们表明，代谢糖标记可以降低 DC 的膜流动性，从而激活 DC，并提高 DC 的抗原呈递和随后的 T 细胞启动特性。代谢糖标记本身可以增强 DC 疫苗的抗肿瘤疗效。此外，通过代谢糖标记引入的细胞表面化学标记物（例如叠氮基团）还可以使过继转移的 DC 进行细胞因子的体内缀合，从而进一步增强 CTL 反应和抗肿瘤疗效。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，对临床制造过程的干扰最小。
