Sheida Shariat - Department of Pharmaceutics, School of Pharmacy, Shahid Beheshti University of Medical Sciences, Tehran, Iran
Ali Badiee - Nanotechnology Research Center, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran
Seyed Amir Jalali - Department of Immunology, Medical School, Shahid Beheshti University of Medical Sciences, Tehran, Iran
Mercedeh Mansourian - Nanotechnology Research Center, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran
Seyed Alireza Mortazavi - Department of Pharmaceutics, School of Pharmacy, Shahid Beheshti University of Medical Sciences, Tehran, Iran
Mahmoud Reza Jaafari - Biotechnology Research Center, Nanotechnology Research Center, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran

Objective(s):Tumor-associated antigen (TAA) subunit-based vaccines constitute promising tools for anticancer immunotherapy. However, a major limitation in the development of such vaccines is the poor immunogenicity of peptides when used alone.The aim of this study was to develop an efficient vaccine delivery system and adjuvant to enhance anti-tumor activity of a synthetic HER۲/neu derived peptide (P۵). Materials and Methods: P۵ peptide was encapsulated with different liposomal formulations composed of DMPC:DMPG:Chol:DOPE and loaded with monophosphoryl lipid A (MPL). All formulations were characterized for their physicochemical properties. To evaluate vaccine efficacy, BALB/c mice were first immunized with free peptide or liposomal formulations, then, inoculated with a subcutaneous injection of TUBO tumor cells. Enzyme-linked immunospot, cytotoxicity and intracellular cytokine assays, as well as tumor size and animal survival analysis, were performed to evaluate the immune responses. Results: The results demonstrated that P۵ encapsulated into liposomal formulations was not able to induce CD۸ and CD۴ T cells to produce IFN-γ. That is why, a potent CTL response and antitumor immunity was not induced. Conclusion: The Lip-DOPE-P۵-MPL formulation in spite of using pH-sensitive lipid to direct intracellular trafficking of peptide to MHC I presentation pathway and MPL to enhance peptide adjuvanticity was interesting. The failure in inducing anti-tumor immunity may be attributed to low uptake of anionic conventional liposomes by dendritic cells (DCs) that have negative surface charge.

Breast Cancer, CTL epitope, HER۲/neu peptide, Peptide vaccine, pH-sensitive liposome