title: GTL001, a bivalent therapeutic vaccine against human papillomavirus 16 and 18, induces antigen-specific CD8+ T cell responses leading to tumor regression.
abstract: BACKGROUND
  Prophylactic vaccines are available for women and girls not yet infected with HPV, but women already infected with HPV need a treatment to prevent progression to high-grade cervical lesions and cancer. GTL001 is a bivalent therapeutic vaccine for eradicating HPV-infected cells that contains HPV16 E7 and HPV18 E7 both fused to detoxified adenylate cyclase from Bordetella pertussis, which binds specifically to CD11b+ antigen-presenting cells. This study examined the ability of therapeutic vaccination with GTL001 adjuvanted with topical imiquimod cream to induce functional HPV16 E7- and HPV18 E7-specific CD8+ T cell responses.
  
  
  METHODS
  Binding of GTL001 to human CD11b was assessed by a cell-based competition binding assay. Cellular immunogenicity of intradermal vaccination with GTL001 was assessed in C57BL/6 mice by enzyme-linked immunospot assay and in vivo killing assays. In vivo efficacy of GTL001 vaccination was investigated in the TC-1 murine HPV16 E7-expressing tumor model.
  
  
  RESULTS
  GTL001 bound specifically to the human CD11b/CD18 receptor. GTL001 adjuvanted with topical 5% imiquimod cream induced HPV16 E7 and HPV18 E7-specific CD8+ T cell responses. This CD8+ T-cell response mediated in vivo killing of HPV E7-expressing cells. In the HPV16 E7-expressing tumor model, GTL001 adjuvanted with imiquimod but not imiquimod alone or a combination of unconjugated HPV16 E7 and HPV18 E7 caused complete tumor regression.
  
  
  CONCLUSIONS
  GTL001 adjuvanted with topical 5% imiquimod is immunogenic and induces HPV16 E7 and HPV18 E7-specific CD8+ T cell responses that can kill HPV E7-expressing cells and eliminate HPV E7-expressing tumors.
authors.affiliation: Genticel, Labège, France.
authors.forename: Michaël
authors.initials: M
authors.lastname: Esquerré
authors.affiliation: Genticel, Paris, France.
authors.forename: Myriam
authors.initials: M
authors.lastname: Bouillette-Marussig
authors.affiliation: Genticel, Labège, France.
authors.forename: Anne
authors.initials: A
authors.lastname: Goubier
authors.affiliation: Genticel, Labège, France.
authors.forename: Marie
authors.initials: M
authors.lastname: Momot
authors.affiliation: Genticel, Labège, France.
authors.forename: Christophe
authors.initials: C
authors.lastname: Gonindard
authors.affiliation: Genticel, Labège, France.
authors.forename: Hélène
authors.initials: H
authors.lastname: Keller
authors.affiliation: Genticel, Labège, France.
authors.forename: Astrid
authors.initials: A
authors.lastname: Navarro
authors.affiliation: Genticel, Paris, France.
authors.forename: Marie-Christine
authors.identifier: http://orcid.org/0000-0001-7202-8844
authors.initials: MC
authors.lastname: Bissery
mesh_terms: D000276:Adjuvants, Immunologic / Q000008:administration & dosage; D000634:Aminoquinolines / Q000008:administration & dosage; D000818:Animals; D000956:Antigens, Viral / Q000276:immunology*; D039481:CD11b Antigen / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D016466:CHO Cells; D003412:Cricetulus; D005260:Female; D000077271:Imiquimod; D051379:Mice; D008810:Mice, Inbred C57BL; D053918:Papillomavirus Vaccines / Q000276:immunology*
chemical_list: D000276:Adjuvants, Immunologic; D000634:Aminoquinolines; D000956:Antigens, Viral; D039481:CD11b Antigen; C509295:ITGAM protein, human; D053918:Papillomavirus Vaccines; D000077271:Imiquimod