Title:Stimulation of Tumor-Specific Immunity by p5 HER-2/neu Generated Peptide Encapsulated in Nano-liposomes with High Phase Transition Temperature Phospholipids
Volume: 14
Issue: 4
Author(s): Mona Yazdani, Seyed Amir Jalali, Ali Badiee, Sheida Shariat, Mercedeh Mansourian, Leila Arabi, Azam Abbasi, Zahra Saberi and Mahmoud Reza Jaafari*
Affiliation:
- Biotechnology Research Center, Nanotechnology Research Center, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad,Iran
Keywords:
Cancer vaccine, cell mediated immunity, liposomes, nanoliposomes, P5 HER2/neu peptide, phase transition temperature.
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.