title: Eradication of established tumors by vaccination with Venezuelan equine encephalitis virus replicon particles delivering human papillomavirus 16 E7 RNA.
abstract: The etiological role of human papillomaviruses (HPV) in cervical and other cancers suggests that therapeutic vaccines directed against requisite viral antigens may eradicate tumors or their precursors. A Venezuelan equine encephalitis (VEE) alphavirus vector delivering the HPV16 E7 RNA was evaluated for antitumor efficacy using a murine E7+ tumor model. Vaccination with VEE replicon particles expressing E7 (E7-VRP) induced class I-restricted CD8+ T-cell responses as determined by IFN-gamma enzyme-linked immunospot (ELISPOT), tetramer, and cytotoxicity assays. E7-VRP vaccination prevented tumor development in all of the mice and effectively eliminated 7-day established tumors in 67% of tumor-bearing mice. The induction of protective T-cell responses was dependent on CD8+, but not CD4+ T cells. Long-lasting T-cell memory responses developed in E7-VRP-vaccinated mice as determined by complete protection from tumor challenge 3 months after the final vaccination. These promising results highlight the potent CD8+ T-cell-mediated antitumor effects elicited by VEE replicon-based vectors and support their further development toward clinical testing against cervical intraepithelial neoplasia or carcinoma.
authors.affiliation: Cardinal Bernardin Cancer Center, Loyola University-Chicago, Maywood, Illinois 60153, USA.
authors.forename: M P
authors.initials: MP
authors.lastname: Velders
authors.forename: S
authors.initials: S
authors.lastname: McElhiney
authors.forename: M C
authors.initials: MC
authors.lastname: Cassetti
authors.forename: G L
authors.initials: GL
authors.lastname: Eiben
authors.forename: T
authors.initials: T
authors.lastname: Higgins
authors.forename: G R
authors.initials: GR
authors.lastname: Kovacs
authors.forename: A G
authors.initials: AG
authors.lastname: Elmishad
authors.forename: W M
authors.initials: WM
authors.lastname: Kast
authors.forename: L R
authors.initials: LR
authors.lastname: Smith
mesh_terms: D000818:Animals; D019496:Cancer Vaccines / Q000235:genetics* / Q000276:immunology*; D004666:Encephalitis Virus, Venezuelan Equine / Q000235:genetics* / Q000276:immunology; D005260:Female; D015316:Genetic Therapy / Q000379:methods; D005822:Genetic Vectors / Q000235:genetics; D007156:Immunologic Memory / Q000276:immunology; D007371:Interferon-gamma / Q000096:biosynthesis / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009374:Neoplasms, Experimental / Q000235:genetics / Q000276:immunology / Q000628:therapy*; D009856:Oncogene Proteins, Viral / Q000235:genetics* / Q000276:immunology*; D050725:Papillomavirus E7 Proteins; D012367:RNA, Viral / Q000008:administration & dosage / Q000235:genetics*; D012093:Replicon / Q000235:genetics* / Q000276:immunology; D016176:T-Lymphocyte Subsets / Q000276:immunology; D014614:Vaccines, Synthetic / Q000235:genetics / Q000276:immunology
chemical_list: D019496:Cancer Vaccines; D009856:Oncogene Proteins, Viral; D050725:Papillomavirus E7 Proteins; D012367:RNA, Viral; D014614:Vaccines, Synthetic; C059731:oncogene protein E7, Human papillomavirus type 16; D007371:Interferon-gamma