title: Effective induction of anti-tumor immunity using p5 HER-2/neu derived peptide encapsulated in fusogenic DOTAP cationic liposomes co-administrated with CpG-ODN.
abstract: Cationic liposomes have been used as efficient antigen delivery systems for cancer vaccination. The current study has investigated whether the incorporation of the helper-fusogenic lipid dioleoylphosphatidylethanolamine (DOPE) in cationic liposomes composed of 1,2-dioleoyl-3-trimethylammonium propane (DOTAP)-cholesterol enhances the cytosolic delivery of p5 HER-2/neu derived peptide (p5) and promotes cytotoxic T lymphocytes (CTL) response. The p5, which is a very hydrophobic peptide, was encapsulated into liposomes by using three different methods and characterized for their colloidal properties. A chaotropic loading method using 7 M urea provided the highest encapsulation yields. Mice were first immunized with encapsulated p5 in liposomes composed of either DOTAP-cholesterol or DOTAP-cholesterol-DOPE, alone or co-administered with CpG-ODN, as an immunoadjuvant, then, inoculated with a subcutaneous injection of TUBO tumor cells. Results obtained from enzyme-linked immunospot, cytotoxicity and intracellular cytokine assays as well as tumor sizes and animal survival analysis demonstrated that p5 encapsulated in DOTAP-cholesterol-DOPE liposomes co-administered with CpG-ODN greatly enhanced the cytotoxic T lymphocytes response and highly inhibited the tumor progression. The outperformance of DOTAP-cholesterol-DOPE liposomes+CpG-ODN was found to be attributed to its capability in induction of both CD8+ and CD4+ responses. This formulation could be a suitable vaccine candidate against Her2 positive cancers and merits further investigations.
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: Nanotechnology Research Center, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran. Electronic address: BadieeA@mums.ac.ir.
authors.forename: Ali
authors.initials: A
authors.lastname: Badiee
authors.affiliation: Nanotechnology Research Center, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran; Immunogenetic and Cell Culture Department, Immunology Research Center, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.
authors.forename: Seyed Amir
authors.initials: SA
authors.lastname: Jalali
authors.affiliation: Nanotechnology Research Center, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, 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: Mona
authors.initials: M
authors.lastname: Yazdani
authors.affiliation: Nanotechnology Research Center, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran.
authors.forename: Mohamdreza
authors.initials: M
authors.lastname: Amin
authors.affiliation: Biotechnology Research Center, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran; Nanotechnology Research Center, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran. Electronic address: Jafarimr@mums.ac.ir.
authors.forename: Mahmoud Reza
authors.initials: MR
authors.lastname: Jaafari
mesh_terms: D000276:Adjuvants, Immunologic / Q000008:administration & dosage; D000818:Animals; D019496:Cancer Vaccines / Q000008:administration & dosage / Q000276:immunology; D045744:Cell Line, Tumor; D016207:Cytokines / Q000096:biosynthesis; D003602:Cytotoxicity, Immunologic; D004195:Disease Models, Animal; D005229:Fatty Acids, Monounsaturated; D005260:Female; D006801:Humans; D007114:Immunization; D008081:Liposomes; D051379:Mice; D009369:Neoplasms / Q000276:immunology / Q000378:metabolism / Q000401:mortality / Q000473:pathology / Q000628:therapy; D009838:Oligodeoxyribonucleotides / Q000008:administration & dosage* / Q000276:immunology*; D010446:Peptide Fragments / Q000008:administration & dosage* / Q000276:immunology*; D000644:Quaternary Ammonium Compounds; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000737:chemistry / Q000276:immunology*; D013154:Spleen / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism; D047368:Tumor Burden
chemical_list: D000276:Adjuvants, Immunologic; D019496:Cancer Vaccines; D016207:Cytokines; D005229:Fatty Acids, Monounsaturated; D008081:Liposomes; D009838:Oligodeoxyribonucleotides; D010446:Peptide Fragments; D000644:Quaternary Ammonium Compounds; D018719:Erb-b2 Receptor Tyrosine Kinases; C408982:CPG-oligonucleotide; C070046:1,2-dioleoyloxy-3-(trimethylammonium)propane
keywords: Breast cancer; CTL epitope; Cationic liposome; Fusogenic liposome; HER2/neu peptide; Peptide vaccine