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, Mahmoud Reza Jaafari*

Journal Name: Current Drug Delivery

Volume 14 , Issue 4 , 2017

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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.

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Article Details

VOLUME: 14
ISSUE: 4
Year: 2017
Page: [492 - 502]
Pages: 11
DOI: 10.2174/1567201813666160712164149
Price: $65

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