title: Efficacy of DNA vaccines forming e7 recombinant retroviral virus-like particles for the treatment of human papillomavirus-induced cancers.
abstract: Human papillomavirus (HPV) is involved in the development of anogenital tumors and also in the development of oropharyngeal head and neck carcinomas, where HPV-16, expressing the E6 and E7 oncoproteins, is the most frequent serotype. Although vaccines encoding L1 and L2 capsid HPV proteins are efficient for the prevention of HPV infection, they are inadequate for treating established tumors. Hence, development of innovative vaccine therapies targeting E6/E7 is important for controlling HPV-induced cancers. We have engineered a nononcogenic mutated E7-specific plasmo-retroVLP vaccine (pVLP-E7), consisting of plasmid DNA, that is able to form recombinant retrovirus-based virus-like particles (VLPs) that display E7 antigen into murine leukemia virus Gag proteins pseudotyped with vesicular stomatitis virus envelope glycoprotein (VSV-G). pVLP-E7 vaccinations were studied for their ability to generate specific immune responses and for induction of protective immunity against tumor cell challenge in preventive and therapeutic models. The produced VLPs induce the maturation of human dendritic cells in vitro and mount specific E7 T cell responses. Intradermic vaccinations of mice with pVLP-E7 show their efficacy to generate antigen-specific T cell responses, to prevent and protect animals from early TC-1 tumor development compared with standard DNA or VLP immunizations. The vaccine efficacy was also evaluated for advanced tumors in mice vaccinated at various time after the injection of TC-1 cells. Data show that pVLP-E7 vaccination can cure mice with already established tumors only when combined with Toll-like receptor-7 (TLR7) and TLR9 agonists. Our findings provide evidence that pVLPs, combining the advantages of DNA and VLP vaccines, appear to be a promising strategy for the treatment of HPV-induced cancers.
authors.affiliation: Research Unit UMR CNRS 7211/INSERM 959, 75013 Paris, France.
authors.forename: Geraldine
authors.initials: G
authors.lastname: Lescaille
authors.forename: Fabien
authors.initials: F
authors.lastname: Pitoiset
authors.forename: Rodney
authors.initials: R
authors.lastname: Macedo
authors.forename: Claude
authors.initials: C
authors.lastname: Baillou
authors.forename: Christophe
authors.initials: C
authors.lastname: Huret
authors.forename: David
authors.initials: D
authors.lastname: Klatzmann
authors.forename: Eric
authors.initials: E
authors.lastname: Tartour
authors.forename: François M
authors.initials: FM
authors.lastname: Lemoine
authors.forename: Bertrand
authors.initials: B
authors.lastname: Bellier
mesh_terms: D000818:Animals; D036022:Capsid Proteins / Q000235:genetics / Q000276:immunology; D045744:Cell Line, Tumor; D052162:Human papillomavirus 16 / Q000235:genetics / Q000276:immunology; D006801:Humans; D051379:Mice; D009369:Neoplasms / Q000235:genetics / Q000628:therapy* / Q000821:virology*; D009856:Oncogene Proteins, Viral / Q000235:genetics* / Q000276:immunology; D050725:Papillomavirus E7 Proteins / Q000235:genetics / Q000276:immunology; D012097:Repressor Proteins / Q000235:genetics* / Q000276:immunology; D019444:Vaccines, DNA / Q000008:administration & dosage* / Q000276:immunology; D058425:Vaccines, Virus-Like Particle / Q000008:administration & dosage / Q000276:immunology
chemical_list: D036022:Capsid Proteins; C068651:E6 protein, Human papillomavirus type 16; D009856:Oncogene Proteins, Viral; D050725:Papillomavirus E7 Proteins; D012097:Repressor Proteins; D019444:Vaccines, DNA; D058425:Vaccines, Virus-Like Particle; C059731:oncogene protein E7, Human papillomavirus type 16; C063317:L1 protein, Human papillomavirus type 16