Conjugated Nanoliposome With the Her2/ Neu-Derived Peptide Gp2 As an Effective Vaccine Against Breast Cancer in Mice Xenograft Model Publisher Pubmed



Razazan A^{1, 2, 3} ; Behravan J^{3, 4} ; Arab A^{2, 3, 4} ; Barati N^{2, 3, 4} ; Arabi L^{2, 3, 4} ; Gholizadeh Z⁵ ; Hatamipour M^{2, 4} ; Nikpoor AR⁵ ; Momtaziborojeni AA^{2, 6} ; Mosaffa F^{3, 4} ; Ghahremani MH¹ ; Jaafari MR^{2, 3, 4} Show Affiliations
Source: PLoS ONE Published:2017

Abstract

One of the challenging issues in vaccine development is peptide and adjuvant delivery into target cells. In this study, we developed a vaccine and therapeutic delivery system to increase cytotoxic T lymphocyte (CTL) response against a breast cancer model overexpres-sing HER2/neu. Gp2, a HER2/neu-derived peptide, was conjugated to Maleimide-mPEG2000-DSPE micelles and post inserted into liposomes composed of DMPC, DMPG phospholipids, and fusogenic lipid dioleoylphosphatidylethanolamine (DOPE) containing monophosphoryl lipid A (MPL) adjuvant (DMPC-DMPG-DOPE-MPL-Gp2). BALB/c mice were immunized with different formulations and the immune response was evaluated in vitro and in vivo. ELISpot and intracellular cytokine analysis by flow cytometry showed that the mice vaccinated with Lip-DOPE-MPL-GP2 incited the highest number of IFN-γ+ in CD8+ cells and CTL response. The immunization led to lower tumor sizes and longer survival time compared to the other groups of mice immunized and treated with the Lip-DOPE-MPL-GP2 formulation in both prophylactic and therapeutic experiments. These results showed that co-formulation of DOPE and MPL conjugated with GP2 peptide not only induces high antitumor immunity but also enhances therapeutic efficacy in TUBO mice model. Lip-DOPE-MPL-GP2 formulation could be a promising vaccine and a therapeutic delivery system against HER2 positive cancers and merits further investigation. © 2017 Razazan et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.