title: TriVax-HPV: an improved peptide-based therapeutic vaccination strategy against human papillomavirus-induced cancers.
abstract: BACKGROUND
  Therapeutic vaccines for cancer are an attractive alternative to conventional therapies, since the later result in serious adverse effects and in most cases are not effective against advanced disease. Human papillomavirus (HPV) is responsible for several malignancies such as cervical carcinoma. Vaccines targeting oncogenic viral proteins like HPV16-E6 and HPV16-E7 are ideal candidates to elicit strong immune responses without generating autoimmunity because: (1) these products are not expressed in normal cells and (2) their expression is required to maintain the malignant phenotype. Our group has developed peptide vaccination strategy called TriVax, which is effective in generating vast numbers of antigen-specific T cells in mice capable of persisting for long time periods.
  
  
  METHODS
  We have used two HPV-induced mouse cancer models (TC-1 and C3.43) to evaluate the immunogenicity and therapeutic efficacy of TriVax prepared with the immunodominant CD8 T-cell epitope HPV16-E7(49-57), mixed with poly-IC adjuvant and costimulatory anti-CD40 antibodies.
  
  
  RESULTS
  TriVax using HPV16-E7(49-57) induced large and persistent T-cell responses that were therapeutically effective against established HPV16-E7 expressing tumors. In most cases, TriVax was successful in attaining complete rejections of 6-11-day established tumors. In addition, TriVax induced long-term immunological memory, which prevented tumor recurrences. The anti-tumor effects of TriVax were independent of NK and CD4 T cells and, surprisingly, did not rely to a great extent on type-I or type-II interferon.
  
  
  CONCLUSIONS
  These findings indicate that the TriVax strategy is an appealing immunotherapeutic approach for the treatment of established viral-induced tumors. We believe that these studies may help to launch more effective and less invasive therapeutic vaccines for HPV-mediated malignancies.
authors.affiliation: Department of Molecular Medicine, University of South Florida, Tampa, FL, USA.
authors.forename: Kelly
authors.initials: K
authors.lastname: Barrios
authors.forename: Esteban
authors.initials: E
authors.lastname: Celis
mesh_terms: D000818:Animals; D003226:Congresses as Topic; D004195:Disease Models, Animal; D018984:Epitopes, T-Lymphocyte / Q000276:immunology / Q000627:therapeutic use; D005260:Female; D016056:Immunodominant Epitopes / Q000276:immunology / Q000627:therapeutic use; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009374:Neoplasms, Experimental / Q000276:immunology* / Q000821:virology*; D050725:Papillomavirus E7 Proteins / Q000276:immunology* / Q000627:therapeutic use; D030361:Papillomavirus Infections / Q000150:complications; D053918:Papillomavirus Vaccines / Q000276:immunology / Q000627:therapeutic use*
chemical_list: D018984:Epitopes, T-Lymphocyte; D016056:Immunodominant Epitopes; D050725:Papillomavirus E7 Proteins; D053918:Papillomavirus Vaccines; C059731:oncogene protein E7, Human papillomavirus type 16