title: Polyacrylate-based delivery system for self-adjuvanting anticancer peptide vaccine.
abstract: Vaccination can provide a safe alternative to chemotherapy by using the body's natural defense mechanisms to create a potent immune response against tumor cells. Peptide-based therapeutic vaccines against human papillomavirus (HPV)-related cancers are usually designed to elicit cytotoxic T cell responses by targeting the HPV-16 E7 oncoprotein. However, peptides alone lack immunogenicity, and an additional adjuvant or external delivery system is required. In this study, we developed new polymer-peptide conjugates to create an efficient self-adjuvanting system for peptide-based therapeutic vaccines. These conjugates reduced tumor growth and eradicated E7-positive TC-1 tumors in mice after a "single shot" immunization, without the help from an external adjuvant. The new conjugates had a significantly higher anticancer efficacy than the antigen formulated with a commercial adjuvant. Furthermore, the polymer-peptide conjugates were promptly taken up by antigen presenting cells, including dendritic cells and macrophages, and efficiently activated CD4(+) T-helper cells and CD8(+) cytotoxic T lymphocyte cells.
authors.affiliation: School of Chemistry and Molecular Biosciences, ‡Australian Institute for Bioengineering and Nanotechnology, and §School of Pharmacy, The University of Queensland , Brisbane, QLD 4072, Australia.
authors.forename: Tzu-Yu
authors.initials: TY
authors.lastname: Liu
authors.forename: Waleed M
authors.initials: WM
authors.lastname: Hussein
authors.forename: Ashwini Kumar
authors.initials: AK
authors.lastname: Giddam
authors.forename: Zhongfan
authors.initials: Z
authors.lastname: Jia
authors.forename: Jennifer M
authors.initials: JM
authors.lastname: Reiman
authors.forename: Mehfuz
authors.initials: M
authors.lastname: Zaman
authors.forename: Nigel A J
authors.initials: NA
authors.lastname: McMillan
authors.forename: Michael F
authors.initials: MF
authors.lastname: Good
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Monteiro
authors.forename: Istvan
authors.initials: I
authors.lastname: Toth
authors.forename: Mariusz
authors.initials: M
authors.lastname: Skwarczynski
mesh_terms: D000180:Acrylic Resins / Q000008:administration & dosage*; D000818:Animals; D019496:Cancer Vaccines / Q000276:immunology*; D003713:Dendritic Cells / Q000276:immunology; D016503:Drug Delivery Systems; D005260:Female; D008213:Lymphocyte Activation; D008264:Macrophages / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D009374:Neoplasms, Experimental / Q000628:therapy* / Q000821:virology; D050725:Papillomavirus E7 Proteins / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology; D022223:Vaccines, Subunit / Q000276:immunology
chemical_list: D000180:Acrylic Resins; D019496:Cancer Vaccines; D050725:Papillomavirus E7 Proteins; D022223:Vaccines, Subunit; C059731:oncogene protein E7, Human papillomavirus type 16; C006903:carbopol 940