Eradication of established HPV16-transformed tumours after immunisation with recombinant Semliki Forest virus expressing a fusion protein of E6 and E7.
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.
Daemen
Toos
T
Department of Medical Microbiology, Molecular Virology Section, University of Groningen, Groningen, The Netherlands. c.a.h.h.daemen@med.rug.nl
Riezebos-Brilman
Annelies
A
Bungener
Laura
L
Regts
Joke
J
Dontje
Bert
B
Wilschut
Jan
J
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*
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