title: Eradication of established HPV16-transformed tumours after immunisation with recombinant Semliki Forest virus expressing a fusion protein of E6 and E7.
abstract: Previously, we described the efficacy of immunisation with recombinant Semliki Forest virus (SFV), expressing the human papillomavirus 16 (HPV) oncoproteins E6 and E7, in inducing HPV-specific CTLs and anti-tumour responses. Recently, we developed a novel recombinant SFV construct encoding a relatively stable fusion protein of HPV16 E6 and E7 under control of a translational enhancer derived from the SFV capsid protein. In the present study we demonstrate that immunisation of tumour-bearing mice with this improved vector results in the regression and complete elimination of established tumours. We furthermore demonstrate that a long-term high level of CTL activity, up to 340 days, accompanies the anti-tumour response. Thus, immunisation with recombinant SFV particles encoding increased levels of a fusion protein of HPV16 E6 and E7 efficiently induces CTL activity and CTL memory resulting in a potent therapeutic anti-tumour effect.
authors.affiliation: Department of Medical Microbiology, Molecular Virology Section, University of Groningen, Groningen, The Netherlands. c.a.h.h.daemen@med.rug.nl
authors.forename: Toos
authors.initials: T
authors.lastname: Daemen
authors.forename: Annelies
authors.initials: A
authors.lastname: Riezebos-Brilman
authors.forename: Laura
authors.initials: L
authors.lastname: Bungener
authors.forename: Joke
authors.initials: J
authors.lastname: Regts
authors.forename: Bert
authors.initials: B
authors.lastname: Dontje
authors.forename: Jan
authors.initials: J
authors.lastname: Wilschut
mesh_terms: D000818:Animals; D002460:Cell Line / Q000821:virology; D006224:Cricetinae; D003602:Cytotoxicity, Immunologic; D005260:Female; D007156:Immunologic Memory; D008647:Mesocricetus; D051379:Mice; D008810:Mice, Inbred C57BL; D009374:Neoplasms, Experimental / Q000188:drug therapy* / Q000821:virology; D009856:Oncogene Proteins, Viral / Q000235:genetics / Q000276:immunology*; D027383:Papillomaviridae / Q000235:genetics / Q000276:immunology*; D050725:Papillomavirus E7 Proteins; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000276:immunology; D012097:Repressor Proteins; D012672:Semliki forest virus / Q000235:genetics / Q000276:immunology*; D014407:Tumor Cells, Cultured / Q000637:transplantation; D014614:Vaccines, Synthetic / Q000276:immunology / Q000627:therapeutic use; D014765:Viral Vaccines / Q000276:immunology / Q000627:therapeutic use*
chemical_list: C068651:E6 protein, Human papillomavirus type 16; D009856:Oncogene Proteins, Viral; D050725:Papillomavirus E7 Proteins; D011993:Recombinant Fusion Proteins; D012097:Repressor Proteins; D014614:Vaccines, Synthetic; D014765:Viral Vaccines; C059731:oncogene protein E7, Human papillomavirus type 16