title: Preparation and characterization of different liposomal formulations containing P5 HER2/neu-derived peptide and evaluation of their immunological responses and antitumor effects.
abstract: OBJECTIVE
  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 HER2/neu derived peptide (P5).
  
  
  METHODS
  P5 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 P5 encapsulated into liposomal formulations was not able to induce CD8 and CD4 T cells to produce IFN-γ. That is why, a potent CTL response and antitumor immunity was not induced.
  
  
  CONCLUSIONS
  The Lip-DOPE-P5-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.
authors.affiliation: Department of Pharmaceutics, School of Pharmacy, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
authors.forename: Sheida
authors.initials: S
authors.lastname: Shariat
authors.affiliation: Nanotechnology Research Center, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran.
authors.forename: Ali
authors.initials: A
authors.lastname: Badiee
authors.affiliation: Department of Immunology, Medical School, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
authors.forename: Seyed
authors.initials: S
authors.lastname: Amir Jalali
authors.affiliation: Nanotechnology Research Center, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran.
authors.forename: Mercedeh
authors.initials: M
authors.lastname: Mansourian
authors.affiliation: Department of Pharmaceutics, School of Pharmacy, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
authors.forename: Seyed
authors.initials: S
authors.lastname: Alireza Mortazavi
authors.affiliation: Biotechnology Research Center, Nanotechnology Research Center, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran.
authors.forename: Mahmoud
authors.initials: M
authors.lastname: Reza Jaafari
keywords: Breast cancer; CTL epitope; HER2/neu peptide; Peptide vaccine; pH-sensitive liposome