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Antitumor activity of liposomal ErbB2/HER2 epitope peptide-based vaccine constructs incorporating TLR agonists and mannose receptor targeting

Paper ID Volume ID Publish Year Pages File Format Full-Text
7690 560 2011 10 PDF Available
Title
Antitumor activity of liposomal ErbB2/HER2 epitope peptide-based vaccine constructs incorporating TLR agonists and mannose receptor targeting
Abstract

Synthetic and molecularly defined constructs containing the minimal components to mimic and amplify the physiological immune response are able to induce an efficient cytotoxic response. In the current study this approach was applied to the development of highly versatile liposomal constructs to co-deliver peptide epitopes in combination with TLR agonists in order to induce a specific anti-tumor cellular immune response against ErbB2 protein-expressing tumor cells. Liposomes containing ErbB2 p63–71 cytotoxic T lymphocyte (CTL) and HA307-319 T- helper (Th) peptide epitopes associated to innovative synthetic TLR2/1 (Pam3CAG) or TLR2/6 agonists (Pam2CAG and Pam2CGD), were injected in mice bearing ErbB2 protein-expressing tumor cells. Mannosylated ligands were also incorporated into the constructs to target antigen-presenting cells. We showed that the TLR2/6 agonists were more efficient than the TLR2/1 agonists for the eradication of tumors expressing ErbB2 protein. Furthermore, mannose-targeted liposomes displayed higher therapeutic efficiency against tumor allowing treatment with decreased quantities of both TLR ligands and peptide epitopes. Our results validated that antigen-associated mannosylated liposomes combined with efficient TLR ligands are effective vectors for vaccination against tumor. In this study we developed useful tools to evaluate the vaccination efficiency of various adjuvants and/or targeting molecules and their potential synergy.

Keywords
Liposome; Cancer vaccine; Peptide-based vaccine; Dendritic cell targeting; TLR ligandsAPC, antigen-presenting cells; BCA, bicinchoninic acid; Chol, cholesterol; DC, dendritic cell; DDS, drug delivery system; DOG(Man)2, dioleylglycerol-dimannosylated ancho
First Page Preview
Antitumor activity of liposomal ErbB2/HER2 epitope peptide-based vaccine constructs incorporating TLR agonists and mannose receptor targeting
Publisher
Database: Elsevier - ScienceDirect
Journal: Biomaterials - Volume 32, Issue 20, July 2011, Pages 4574–4583
Authors
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Subjects
Physical Sciences and Engineering Chemical Engineering Bioengineering