Coordinating antigen cytosolic delivery and danger signaling to program potent cross-priming by micelle-based nanovaccine.
Coordinating antigen cytosolic delivery and danger signaling to program potent cross-priming by micelle-based nanovaccine.
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DOI：
10.1038/celldisc.2017.7
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发表时间：
2017
期刊：
影响因子：
33.5
通讯作者：
Liang W
中科院分区：
文献类型：
--
作者：
Liu Z;Zhou C;Qin Y;Wang Z;Wang L;Wei X;Zhou Y;Li Q;Zhou H;Wang W;Fu YX;Zhu M;Liang W
虽然通过检查点阻断重新激活肿瘤组织内的细胞毒性T细胞（CTL）应答在肿瘤免疫治疗中已证明取得了巨大成功，但通过治疗性疫苗主动诱导有效的内源性CTL应答在很大程度上受到抗原的低效胞质递送和淋巴结中树突状细胞（DC）的协调激活的阻碍。在这里，我们表明，聚乙二醇-磷脂酰乙醇胺（PEG-PE）胶束转化为α-螺旋可溶性肽，使其有效的胞质输送。相同的PEG-PE胶束还充当TLR 4信号传导的伴侣以协调其对相同DC的佐剂作用。此外，这些纳米疫苗有效地靶向淋巴结DC。因此，PEG-PE胶束疫苗在多个关键方面进行编程，以诱导强烈的CTL应答，并为联合治疗肿瘤奠定基础。
Although re-activating cytotoxic T-cell (CTLs) response inside tumor tissues by checkpoint blockade has demonstrated great success in tumor immunotherapy, active induction of efficient endogenous CTL response by therapeutic vaccines has been largely hampered by inefficient cytosolic delivery of antigens and coordinated activation of dendritic cells (DCs) in lymph nodes. Here we show that polyethylene glycol-phosphatidylethanolamine (PEG-PE) micelles transform soluble peptides into α-helix to enable their efficient cytosolic delivery. The same PEG-PE micelles also serve as chaperon of TLR4 signaling to coordinate its adjuvant effect on the same DCs. Furthermore, these nanovaccines effectively target lymph node DCs. Thus, PEG-PE micelle vaccines program at multiple key aspects for inducing strong CTL responses and build up a foundation for combinational tumor therapy.