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

Zhida Liu,Luyao Wang,Xiuli Wei,Mingzhao Zhu,Wenjun Wang,Chang Zhou,Hang Zhou,Yan Qin,Qicheng Li,Wei Liang,Yinjian Zhou,Zihao Wang,Yang-Xin Fu

doi:10.1038/celldisc.2017.7

Abstract

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.

Highlights

The importance of cytotoxic T-lymphocyte (CTL) response has been increasingly acknowledged in a series of tumor therapeutic approaches, such as chemotherapy, radiation therapy, antibody mediated targeting therapy and so on [1,2,3,4]
Cytosolic delivery of antigen is favorable for CTL priming through cross-presentation pathway
We have found polyethylene glycol (PEG)-PE micelles is an efficient carrier for cytosolic delivery of antigen peptide

Summary

Introduction

The importance of cytotoxic T-lymphocyte (CTL) response has been increasingly acknowledged in a series of tumor therapeutic approaches, such as chemotherapy, radiation therapy, antibody mediated targeting therapy and so on [1,2,3,4]. It has been further exemplified with recent great success of checkpoint blockade [5, 6]. Many soluble antigenic peptides are non-alpha-helix [17]. For this type of antigens, it is challenging to transform them into α-helix for efficient cytosolic delivery

Methods

Results

Conclusion