PROTAC 工程化蛋白/DNA 纳米抗原是癌症免疫治疗中树突状细胞疫苗的有效增强剂
PROTAC-Engineered Protein/DNA Nanoantigen is a Potent Booster for Dendritic Cell Vaccines in Cancer Immunotherapy.
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题:Metabolic glycan labeling immobilizes dendritic cell membrane and enhances antitumor efficacy of dendritic cell vaccine.
Metabolic glycan labeling immobilizes dendritic cell membrane and enhances antitumor efficacy of dendritic cell vaccine.
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树突状细胞(DC)疫苗是最早获得FDA批准的癌症免疫疗法之一,但其细胞毒性T淋巴细胞(CTL)应答和治疗疗效有限。在此,我们报告一种简便的代谢标记方法,能够对过继转移的DC进行靶向调控,从而开发增强型DC疫苗。我们发现,代谢聚糖标记可以降低DC的膜流动性,从而激活DC并改善DC的抗原呈递及后续T细胞致敏能力。代谢聚糖标记本身即可增强DC疫苗的抗肿瘤疗效。此外,通过代谢聚糖标记引入的细胞表面化学标签(如叠氮基团)还能够实现细胞因子在过继转移DC上的体内偶联,进一步增强了CTL应答和抗肿瘤疗效。我们的DC标记与靶向技术提供了一种提高DC疫苗治疗疗效的策略,且对临床生产过程的干扰极小。
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.
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