title: A prime/boost strategy by DNA/fowlpox recombinants expressing a mutant E7 protein for the immunotherapy of HPV-associated cancers.
abstract: Development of effective therapeutic vaccines against human papilloma virus (HPV) infections remains a priority, considering the high number of new cases of cervical cancer each year by high-risk HPVs, in particular by HPV-16. Vaccines expressing the E7 oncoprotein, which is detectable in all HPV-positive pre-cancerous and cancer cells, might clear already established tumors and support the treatment of HPV-related lesions. In this study, DNA or fowlpox virus recombinants expressing the harmless variant E7GGG of the HPV-16 E7 oncoprotein (DNA(E7GGG) and FP(E7GGG)) were generated. Two immunization regimens were tested in a pre-clinical mouse model by homologous (FP/FP) or heterologous (DNA/FP) prime-boost protocols to evaluate the immune response and therapeutic efficacy of the proposed HPV-16 vaccine. Low levels of anti-E7-specific antibodies were elicited after immunization, and in vivo experiments resulted in a higher number of tumor-free mice after the heterologous immunization. These results establish a preliminary indication for therapy of HPV-related tumors by the combined use of DNA and avipox recombinants, which might represent safer immunogens than vaccinia-based vaccines.
authors.affiliation: Department of Pharmacological Sciences, Università di Milano, Milan, Italy. antonia.radaelli@unimi.it
authors.forename: Antonia
authors.initials: A
authors.lastname: Radaelli
authors.forename: Carlo
authors.initials: C
authors.lastname: De Giuli Morghen
authors.forename: Carlo
authors.initials: C
authors.lastname: Zanotto
authors.forename: Sole
authors.initials: S
authors.lastname: Pacchioni
authors.forename: Massimiliano
authors.initials: M
authors.lastname: Bissa
authors.forename: Rosella
authors.initials: R
authors.lastname: Franconi
authors.forename: Silvia
authors.initials: S
authors.lastname: Massa
authors.forename: Francesca
authors.initials: F
authors.lastname: Paolini
authors.forename: Antonio
authors.initials: A
authors.lastname: Muller
authors.forename: Aldo
authors.initials: A
authors.lastname: Venuti
mesh_terms: D000818:Animals; D019496:Cancer Vaccines / Q000235:genetics / Q000276:immunology / Q000627:therapeutic use*; D002460:Cell Line; D005260:Female; D005587:Fowlpox virus / Q000235:genetics*; D015870:Gene Expression; D052162:Human papillomavirus 16 / Q000235:genetics / Q000276:immunology; D006801:Humans; D007111:Immunity, Cellular; D056724:Immunity, Humoral; D007115:Immunization Schedule; D007167:Immunotherapy; D051379:Mice; D050505:Mutant Proteins / Q000276:immunology; D009369:Neoplasms / Q000276:immunology / Q000628:therapy / Q000821:virology; D050725:Papillomavirus E7 Proteins / Q000235:genetics / Q000276:immunology*; D053918:Papillomavirus Vaccines / Q000235:genetics / Q000627:therapeutic use*; D010957:Plasmids / Q000235:genetics; D019076:Transgenes; D019444:Vaccines, DNA / Q000627:therapeutic use*
chemical_list: D019496:Cancer Vaccines; D050505:Mutant Proteins; D050725:Papillomavirus E7 Proteins; D053918:Papillomavirus Vaccines; D019444:Vaccines, DNA