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Current Drug Delivery

Editor-in-Chief

ISSN (Print): 1567-2018
ISSN (Online): 1875-5704

Research Article

Stimulation of Tumor-Specific Immunity by p5 HER-2/neu Generated Peptide Encapsulated in Nano-liposomes with High Phase Transition Temperature Phospholipids

Author(s): Mona Yazdani, Seyed Amir Jalali, Ali Badiee, Sheida Shariat, Mercedeh Mansourian, Leila Arabi, Azam Abbasi, Zahra Saberi and Mahmoud Reza Jaafari*

Volume 14, Issue 4, 2017

Page: [492 - 502] Pages: 11

DOI: 10.2174/1567201813666160712164149

Price: $65

Abstract

Background: The aim of this study is to evaluate the possible advantages of liposomes with high transition temperature (Tm) in the function of a vaccine for P5 HER2/neu-generated peptide and its adjuvant action to elicit CD8+ T cell response and its efficacy in TUBO in vivo tumor mice model, which over expresses the HER2/neu oncogene. P5, a hydrophobic peptide, was encapsulated in the nanoliposomes consisting of DSPC/DSPG/Chol(Tm 54°C) with a chaotropic loading system via 7M urea and described by size, zeta potential, encapsulation efficiency, and the structural stability of SDS-PAGE.

Methods: We immunized the mice for three times subcutaneously based on a two-week intervals using encapsulated peptide in the nanoliposomes, empty liposome, P5 in PBS, and PBS. Enzyme-linked immunospot assay, cytotoxicity test, and flow cytometric studies followed by the size of tumor and survival time measurements, which were done in TUBO tumor mice version.

Results: Findings of ELISpot and flow cytometric analysis showed that immunization with Lip-p5 nanoliposomes has enhanced the antigen-specific IFN-γ response of CD8+ T cells and induced CTL response, which resulted in a smaller tumor and longer survival time. In addition to increase in amounts of IFN-γ-CD8+ T cells in a group, which was immunized with Lip-P5, our findings also revealed a Th1 shift in the group immunized with an empty liposome with reduced frequencies of IL-4-producing cells and increase of IFN-γ-producing cells.

Conclusion: The results indicated that simple liposomes consisting of phospholipids with high transition temperature could be an effective vaccine vehicle for tumor-associated antigens for inducing cell mediate immunity.

Keywords: Cancer vaccine, cell mediated immunity, liposomes, nanoliposomes, P5 HER2/neu peptide, phase transition temperature.

Graphical Abstract

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