title: Self-Assembling Peptide Epitopes as Novel Platform for Anticancer Vaccination.
abstract: The aim of the present study was to improve the immunogenicity of peptide epitope vaccines using novel nanocarriers based on self-assembling materials. Several studies demonstrated that peptide antigens in nanoparticulate form induce stronger immune responses than their soluble forms. However, several issues such as poor loading and risk of inducing T cell anergy due to premature release of antigenic epitopes have challenged the clinical success of such systems. In the present study, we developed two vaccine delivery systems by appending a self-assembling peptide (Ac-AAVVLLLW-COOH) or a thermosensitive polymer poly(N-isopropylacrylamide (pNIPAm) to the N-terminus of different peptide antigens (OVA250-264, HPV-E743-57) to generate self-assembling peptide epitopes (SAPEs). The obtained results showed that the SAPEs were able to form nanostructures with a diameter from 20 to 200 nm. The SAPEs adjuvanted with CpG induced and expanded antigen-specific CD8+T cells in mice. Furthermore, tumor-bearing mice vaccinated with SAPEs harboring the HPV E743-57peptide showed a delayed tumor growth and an increased survival compared to sham-treated mice. In conclusion, self-assembling peptide based systems increase the immunogenicity of peptide epitope vaccines and therefore warrants further development toward clinical use.
authors.affiliation: Department of Pharmaceutics, Utrecht Institute for Pharmaceutical Sciences, Utrecht University , Utrecht, The Netherlands.|Department of Pharmaceutical Biomaterials and Medical Biomaterials Research Center, Faculty of Pharmacy, Tehran University of Medical Sciences , Tehran, Iran.
authors.forename: Mazda
authors.initials: M
authors.lastname: Rad-Malekshahi
authors.affiliation: Department of Immunohematology and Blood Transfusion, Leiden University Medical Center , Leiden, The Netherlands.
authors.forename: Marieke F
authors.initials: MF
authors.lastname: Fransen
authors.affiliation: Department of Pharmaceutics, Utrecht Institute for Pharmaceutical Sciences, Utrecht University , Utrecht, The Netherlands.
authors.forename: Małgorzata
authors.initials: M
authors.lastname: Krawczyk
authors.affiliation: Department of Pharmaceutics, Utrecht Institute for Pharmaceutical Sciences, Utrecht University , Utrecht, The Netherlands.
authors.forename: Mercedeh
authors.initials: M
authors.lastname: Mansourian
authors.affiliation: Department of Pharmaceutics, Utrecht Institute for Pharmaceutical Sciences, Utrecht University , Utrecht, The Netherlands.
authors.forename: Meriem
authors.initials: M
authors.lastname: Bourajjaj
authors.affiliation: Department of Pharmaceutics, Utrecht Institute for Pharmaceutical Sciences, Utrecht University , Utrecht, The Netherlands.
authors.forename: Jian
authors.initials: J
authors.lastname: Chen
authors.affiliation: Department of Immunohematology and Blood Transfusion, Leiden University Medical Center , Leiden, The Netherlands.
authors.forename: Ferry
authors.initials: F
authors.lastname: Ossendorp
authors.affiliation: Department of Pharmaceutics, Utrecht Institute for Pharmaceutical Sciences, Utrecht University , Utrecht, The Netherlands.
authors.forename: Wim E
authors.identifier: 0000-0002-5750-714X
authors.initials: WE
authors.lastname: Hennink
authors.affiliation: Department of Pharmaceutics, Utrecht Institute for Pharmaceutical Sciences, Utrecht University , Utrecht, The Netherlands.
authors.forename: Enrico
authors.initials: E
authors.lastname: Mastrobattista
authors.affiliation: Department of Pharmaceutics, Utrecht Institute for Pharmaceutical Sciences, Utrecht University , Utrecht, The Netherlands.
authors.forename: Maryam
authors.initials: M
authors.lastname: Amidi
mesh_terms: D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000378:metabolism; D019496:Cancer Vaccines / Q000276:immunology / Q000378:metabolism; D002478:Cells, Cultured; D018984:Epitopes, T-Lymphocyte / Q000276:immunology / Q000378:metabolism*; D007167:Immunotherapy; D051379:Mice; D053758:Nanoparticles / Q000737:chemistry; D010047:Ovalbumin / Q000737:chemistry; D010455:Peptides / Q000276:immunology*; D014611:Vaccination / Q000379:methods
chemical_list: D019496:Cancer Vaccines; D018984:Epitopes, T-Lymphocyte; D010455:Peptides; D010047:Ovalbumin
keywords: human papillomavirus (HPV); immunotherapy; nanoparticles; ovalbumin (OVA); self-assembling peptide epitopes; therapeutic cancer vaccine