title: Role of regulatory T-cells in immunization strategies involving a recombinant alphavirus vector system.
abstract: BACKGROUND
  Regulatory T-cells (Treg) hamper immune responses elicited by cancer vaccines. Therefore, depletion of Treg is being used to improve the outcome of vaccinations.
  
  
  METHODS
  We studied whether an alphavirus vector-based immunotherapeutic vaccine changes the number and/or activity of Treg and if Treg depletion improves the efficacy of this vaccine against tumours. The vaccine is based on a Semliki Forest virus (SFV). The recombinant SFV replicon particles encode a fusion protein of E6 and E7 from human papillomavirus (HPV) type 16 (SFVeE6,7).
  
  
  RESULTS
  We demonstrated that SFVeE6,7 immunization did not change Treg levels and their suppressive activity. Depletion of Treg in mice, using the novel anti-folate receptor 4 antibody, did not enhance the immune response induced by SFVeE6,7 immunization. Both the priming and the proliferation phases of the HPV-specific response elicited with SFVeE6,7 were not affected by the immune-suppressive activity of Treg. Moreover, Treg depletion did not improve the therapeutic antitumour response of SFVeE6,7 in a murine tumour model.
  
  
  CONCLUSIONS
  The efficacy of the SFVeE6,7 vaccine was not hampered by Treg. Therefore, SFVeE6,7 seems a very promising candidate for the treatment of HPV-induced disease, as it may not require additional immune interventions to modulate Treg activity.
authors: Department of Medical Microbiology, Molecular Virology Section, University Medical Center Groningen, University of Groningen, the Netherlands.
authors: Mateusz
authors: M
authors: Walczak
authors: Joke
authors: J
authors: Regts
authors: Antoon J M
authors: AJ
authors: van Oosterhout
authors: Louis
authors: L
authors: Boon
authors: Jan
authors: J
authors: Wilschut
authors: Hans W
authors: HW
authors: Nijman
authors: Toos
authors: T
authors: Daemen
mesh_terms: D000524:Alphavirus; D000818:Animals; D019496:Cancer Vaccines / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*; D005260:Female; D005822:Genetic Vectors / Q000008:administration & dosage / Q000235:genetics* / Q000276:immunology; D006801:Humans; D007114:Immunization / Q000379:methods*; D008213:Lymphocyte Activation; D008212:Lymphocyte Depletion; D051379:Mice; D008810:Mice, Inbred C57BL; D009369:Neoplasms / Q000276:immunology / Q000628:therapy*; D009856:Oncogene Proteins, Viral / Q000235:genetics / Q000276:immunology; D050725:Papillomavirus E7 Proteins / Q000235:genetics / Q000276:immunology; D011995:Recombination, Genetic; D012097:Repressor Proteins / Q000235:genetics / Q000276:immunology; D012672:Semliki forest virus / Q000235:genetics* / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*; D014611:Vaccination
chemical_list: D019496:Cancer Vaccines; C068651:E6 protein, Human papillomavirus type 16; D009856:Oncogene Proteins, Viral; D050725:Papillomavirus E7 Proteins; D012097:Repressor Proteins; C059731:oncogene protein E7, Human papillomavirus type 16