title: Combined synthetic and recombinant techniques for the development of lipoprotein-based, self-adjuvanting vaccines targeting human papillomavirus type-16 associated tumors.
abstract: Human papillomaviruses (HPVs) are associated with various cancers, with HPV16 linked to more than half of cervical cancer cases. Vaccines to prevent HPV infection and cancer development have proven effective, but are not useful in individuals with prior HPV exposure. Treatment vaccines to eradicate or control HPV-associated lesions are therefore desirable for these patients. Herein we describe the development of a process to enable the production of semisynthetic vaccines based on the site-specific attachment of synthetic bacterial lipid analogs (e.g., Pam2Cys) to a non-oncogenic mutant HPV16 E7 protein to generate molecularly defined vaccines. Many cytotoxic lymphocyte (CTL) epitopes from E7 are delivered by this approach; potentially ensuring that large numbers of immunized individuals can generate CTLs to clear HPV infected cells. Delivery of this construct reduced the growth of HPV16-associated tumors in a TC1 mouse model, the effects of which were better than the potent CTL epitope HPV16 E7(44-57) administered with Montanide ISA51 adjuvant.
authors.affiliation: School of Pharmacy, The University of Queensland, 20 Cornwall St, Woolloongabba, QLD 4102, Australia. Electronic address: p.moyle@uq.edu.au.
authors.forename: Peter M
authors.initials: PM
authors.lastname: Moyle
authors.affiliation: School of Chemistry and Molecular Biosciences, The University of Queensland, St Lucia, QLD 4072, Australia.
authors.forename: Wei
authors.initials: W
authors.lastname: Dai
authors.affiliation: School of Chemistry and Molecular Biosciences, The University of Queensland, St Lucia, QLD 4072, Australia.
authors.forename: Tzu-Yu
authors.initials: TY
authors.lastname: Liu
authors.affiliation: School of Chemistry and Molecular Biosciences, The University of Queensland, St Lucia, QLD 4072, Australia; Department of Pharmaceutical Organic Chemistry, Faculty of Pharmacy, Helwan University, Ein Helwan, Helwan, Egypt.
authors.forename: Waleed M
authors.initials: WM
authors.lastname: Hussein
authors.affiliation: The University of Queensland Diamantina Institute, Translational Research Institute (TRI), Woolloongabba, QLD 4102, Australia.
authors.forename: Pirashanthini
authors.initials: P
authors.lastname: Maruthayanar
authors.affiliation: The University of Queensland Diamantina Institute, Translational Research Institute (TRI), Woolloongabba, QLD 4102, Australia.
authors.forename: James W
authors.initials: JW
authors.lastname: Wells
authors.affiliation: Griffith Health Institute and School of Medical Sciences, Griffith University, Southport, QLD 4222, Australia.
authors.forename: Nigel A J
authors.initials: NA
authors.lastname: McMillan
authors.affiliation: School of Chemistry and Molecular Biosciences, The University of Queensland, St Lucia, QLD 4072, Australia.
authors.forename: Mariusz
authors.initials: M
authors.lastname: Skwarczynski
authors.affiliation: School of Pharmacy, The University of Queensland, 20 Cornwall St, Woolloongabba, QLD 4102, Australia; School of Chemistry and Molecular Biosciences, The University of Queensland, St Lucia, QLD 4072, Australia; Institute for Molecular Bioscience, The University of Queensland, St Lucia, QLD 4072, Australia.
authors.forename: Istvan
authors.initials: I
authors.lastname: Toth
mesh_terms: D000276:Adjuvants, Immunologic / Q000138:chemical synthesis / Q000627:therapeutic use*; D000595:Amino Acid Sequence; D000818:Animals; D019496:Cancer Vaccines / Q000138:chemical synthesis / Q000627:therapeutic use*; D060326:Chemistry Techniques, Synthetic; D004591:Electrophoresis, Polyacrylamide Gel; D005260:Female; D006801:Humans; D055666:Lipopeptides / Q000138:chemical synthesis / Q000737:chemistry* / Q000235:genetics; D051379:Mice; D008969:Molecular Sequence Data; D009369:Neoplasms / Q000188:drug therapy*; D050725:Papillomavirus E7 Proteins / Q000187:drug effects*; D030361:Papillomavirus Infections / Q000628:therapy*; D011994:Recombinant Proteins / Q000737:chemistry / Q000235:genetics
chemical_list: D000276:Adjuvants, Immunologic; D019496:Cancer Vaccines; D055666:Lipopeptides; D050725:Papillomavirus E7 Proteins; D011994:Recombinant Proteins; C059731:oncogene protein E7, Human papillomavirus type 16
keywords: Cancer; Human papillomavirus; Pam2Cys; Protein engineering; Vaccine