Eradication of established HPV16-transformed tumours after immunisation with recombinant Semliki Forest virus expressing a fusion protein of E6 and E7

Vaccine. 2003 Mar 7;21(11-12):1082-8. doi: 10.1016/s0264-410x(02)00558-3.

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.

Publication types

  • Evaluation Study

MeSH terms

  • Animals
  • Cell Line / virology
  • Cricetinae
  • Cytotoxicity, Immunologic
  • Female
  • Immunologic Memory
  • Mesocricetus
  • Mice
  • Mice, Inbred C57BL
  • Neoplasms, Experimental / drug therapy*
  • Neoplasms, Experimental / virology
  • Oncogene Proteins, Viral / genetics
  • Oncogene Proteins, Viral / immunology*
  • Papillomaviridae / genetics
  • Papillomaviridae / immunology*
  • Papillomavirus E7 Proteins
  • Recombinant Fusion Proteins / genetics
  • Recombinant Fusion Proteins / immunology
  • Repressor Proteins*
  • Semliki forest virus / genetics
  • Semliki forest virus / immunology*
  • Tumor Cells, Cultured / transplantation
  • Vaccines, Synthetic / immunology
  • Vaccines, Synthetic / therapeutic use
  • Viral Vaccines / immunology
  • Viral Vaccines / therapeutic use*

Substances

  • E6 protein, Human papillomavirus type 16
  • Oncogene Proteins, Viral
  • Papillomavirus E7 Proteins
  • Recombinant Fusion Proteins
  • Repressor Proteins
  • Vaccines, Synthetic
  • Viral Vaccines
  • oncogene protein E7, Human papillomavirus type 16