Coordinating antigen cytosolic delivery and danger signaling to program potent cross-priming by micelle-based nanovaccine

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.