Open AccessCoordinating antigen cytosolic delivery and danger signaling to program potent cross-priming by micelle-based nanovaccine
Author(s) -
Zhida Liu,
Chao Zhou,
Qin Yan,
Zihao Wang,
Luyao Wang,
Xiuli Wei,
Yinjian Zhou,
Qicheng Li,
Hang Zhou,
Wenjun Wang,
Yang Xin Fu,
Mingzhao Zhu,
Wei Liang
Publication year - 2017
Publication title -
cell discovery
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.412
H-Index - 29
ISSN - 2056-5968
DOI - 10.1038/celldisc.2017.7
Subject(s) - ctl* , micelle , chemistry , priming (agriculture) , cross presentation , cytosol , antigen , cytotoxic t cell , adjuvant , microbiology and biotechnology , polyethylene glycol , cancer research , antigen presenting cell , immunology , biology , biochemistry , enzyme , botany , germination , aqueous solution , in vitro
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.