title: Fusion of a tumour-associated antigen to HIV-1 Tat improves protein-based immunotherapy of cancer.
abstract: BACKGROUND
  The ultimate success of cancer vaccination is primarily dependent upon the generation of tumour-specific CTLs. Protein-based vaccination, while safe, poorly elicits such CTL responses. As fusion of an antigen to the HIV-1 Tat transduction domain was reported to increase MHC class I presentation and CTL responses in vitro, we tested the potency of this approach to augment tumour-directed responses.
  
  
  METHODS
  Human papillomavirus type 16 (HPV16) E7 proteins, fused (E7-Tat) or not (E7) to Tat carboxy-terminal region, were produced and studied in vitro and in vivo.
  
  
  RESULTS
  E7-Tat, not E7, penetrated the cell membrane and was transcriptionally active. In vitro, E7-Tat induced higher IFN-gamma production from E7-specific T-cells than E7. In C57BL/6 mice, E7-Tat mixed with Quil A generated enhanced prophylactic and therapeutic suppression of HPV16-positive C3 tumour outgrowth. Similar, but greatly enhanced E7-specific effector and helper T-cell responses were elicited following E7-Tat/Quil A rather than E7/Quil A vaccination.
  
  
  CONCLUSIONS
  This study offers a new strategy for improving subunit cancer vaccines.
authors.affiliation: Institut de Biologie et de Médecine Moléculaires, Université Libre de Bruxelles, Gosselies, Belgium.
authors.forename: Christina
authors.initials: C
authors.lastname: Giannouli
authors.forename: Jean-Marc
authors.initials: JM
authors.lastname: Brulet
authors.forename: Fabienne
authors.initials: F
authors.lastname: Gesché
authors.forename: Jay
authors.initials: J
authors.lastname: Rappaport
authors.forename: Arsène
authors.initials: A
authors.lastname: Burny
authors.forename: Oberdan
authors.initials: O
authors.lastname: Leo
authors.forename: Sophie
authors.initials: S
authors.lastname: Hallez
mesh_terms: D016475:3T3 Cells; D000276:Adjuvants, Immunologic / Q000494:pharmacology; D000818:Animals; D019496:Cancer Vaccines / Q000235:genetics / Q000276:immunology*; D015696:Gene Products, tat / Q000235:genetics / Q000276:immunology*; D007167:Immunotherapy / Q000379:methods*; D007371:Interferon-gamma / Q000096:biosynthesis; D051379:Mice; D008810:Mice, Inbred C57BL; D009374:Neoplasms, Experimental / Q000276:immunology / Q000628:therapy*; D009856:Oncogene Proteins, Viral / Q000235:genetics / Q000276:immunology*; D050725:Papillomavirus E7 Proteins; D062605:Quillaja Saponins; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000276:immunology*; D012503:Saponins / Q000494:pharmacology; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology; D014407:Tumor Cells, Cultured
chemical_list: D000276:Adjuvants, Immunologic; D019496:Cancer Vaccines; D015696:Gene Products, tat; D009856:Oncogene Proteins, Viral; D050725:Papillomavirus E7 Proteins; D062605:Quillaja Saponins; D011993:Recombinant Fusion Proteins; D012503:Saponins; C059731:oncogene protein E7, Human papillomavirus type 16; C046386:Quil A; D007371:Interferon-gamma