title: Multiantigenic peptide-polymer conjugates as therapeutic vaccines against cervical cancer.
abstract: Immunotherapy is one of the most promising strategies for the treatment of cancer. Human papillomavirus (HPV) is responsible for virtually all cases of cervical cancer. The main purpose of a therapeutic HPV vaccine is to stimulate CD8(+) cytotoxic T lymphocytes (CTLs) that can eradicate HPV infected cells. HPV oncoproteins E6 and E7 are continuously expressed and are essential for maintaining the growth of HPV-associated tumor cells. We designed polymer-based multi-antigenic formulations/constructs that were comprised of the E6 and E7 peptide epitopes. We developed an N-terminus-based epitope conjugation to conjugate two unprotected peptides to poly tert-butyl acrylate. This method allowed for the incorporation of the two antigens into a polymeric dendrimer in a strictly equimolar ratio. The most effective formulations eliminated tumors in up to 50% of treated mice. Tumor recurrence was not observed up to 3months post initial challenge.
authors.affiliation: School of Chemistry and Molecular Biosciences, The University of Queensland, St Lucia, Brisbane, QLD 4072, Australia.
authors.forename: Waleed M
authors.initials: WM
authors.lastname: Hussein
authors.affiliation: School of Chemistry and Molecular Biosciences, The University of Queensland, St Lucia, Brisbane, QLD 4072, Australia.
authors.forename: Tzu-Yu
authors.initials: TY
authors.lastname: Liu
authors.affiliation: Australian Institute for Bioengineering and Nanotechnology, The University of Queensland, Brisbane, QLD 4072, Australia.
authors.forename: Zhongfan
authors.initials: Z
authors.lastname: Jia
authors.affiliation: Cancer Research Centre, Griffith Health Institute and School of Medical Science, Griffith University, Gold Coast, QLD 4222, Australia.
authors.forename: Nigel A J
authors.initials: NAJ
authors.lastname: McMillan
authors.affiliation: Australian Institute for Bioengineering and Nanotechnology, The University of Queensland, Brisbane, QLD 4072, Australia.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Monteiro
authors.affiliation: School of Chemistry and Molecular Biosciences, The University of Queensland, St Lucia, Brisbane, QLD 4072, Australia; School of Pharmacy, The University of Queensland, Brisbane, QLD 4072, Australia; Institute for Molecular Bioscience, The University of Queensland, Brisbane, QLD 4072 Australia.
authors.forename: Istvan
authors.initials: I
authors.lastname: Toth
authors.affiliation: School of Chemistry and Molecular Biosciences, The University of Queensland, St Lucia, Brisbane, QLD 4072, Australia. Electronic address: m.skwarczynski@uq.edu.au.
authors.forename: Mariusz
authors.initials: M
authors.lastname: Skwarczynski
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D000941:Antigens / Q000737:chemistry*; D002851:Chromatography, High Pressure Liquid; D000939:Epitopes / Q000737:chemistry / Q000276:immunology; D005260:Female; D051379:Mice; D008810:Mice, Inbred C57BL; D053918:Papillomavirus Vaccines / Q000737:chemistry / Q000276:immunology / Q000627:therapeutic use*; D010455:Peptides / Q000737:chemistry*; D011108:Polymers / Q000737:chemistry*; D021241:Spectrometry, Mass, Electrospray Ionization; D002583:Uterine Cervical Neoplasms / Q000517:prevention & control*
chemical_list: D000941:Antigens; D000939:Epitopes; D053918:Papillomavirus Vaccines; D010455:Peptides; D011108:Polymers
keywords: Cervical cancer; Human papillomavirus; Multiantigenic; Peptide-based subunit vaccine; Polymer–peptide conjugate; Self-adjuvanting; Therapeutic cancer vaccine