title: GTL001, A Therapeutic Vaccine for Women Infected with Human Papillomavirus 16 or 18 and Normal Cervical Cytology: Results of a Phase I Clinical Trial.
abstract: Women infected with human papillomavirus (HPV) with normal cytology to mild abnormalities currently have no treatment options other than watchful waiting or surgery if high-grade cervical lesions or cancer develop. A therapeutic vaccine would offer the possibility of preventing high-grade lesions in HPV-infected women. GTL001 is a therapeutic vaccine composed of recombinant HPV16 and HPV18 E7 proteins fused to catalytically inactive Bordetella pertussis CyaA. This study examined the tolerability and immunogenicity of GTL001 in women infected with HPV16 or HPV18 with normal cytology.
  
  
  
  This was a phase I trial (EudraCT No. 2010-018629-21). In an open-label part, subjects received two intradermal vaccinations 6 weeks apart of 100 or 600 μg GTL001 + topical 5% imiquimod cream at the injection site. In a double-blind part, subjects were randomized 2:1:1 to two vaccinations 6 weeks apart of 600 μg GTL001 + imiquimod, 600 μg GTL001 + placebo cream, or placebo + imiquimod.
  
  
  
  Forty-seven women were included. No dropouts, treatment-related serious adverse events, or dose-limiting toxicities occurred. Local reactions were transient and mostly mild or moderate. HPV16/18 viral load decreased the most in the 600 μg GTL001 + imiquimod group. In post hoc analyses, the 600 μg GTL001 + imiquimod group had the highest rates of initial and sustained HPV16/18 clearance. Imiquimod increased antigen-specific T-cell response rates but not rates of solicited reactions. All subjects seroconverted to CyaA.
  
  
  
  For women infected with HPV16 or HPV18 with normal cervical cytology, GTL001 was immunogenic and had acceptable safety profile. Clin Cancer Res; 22(13); 3238-48. ©2016 AACR.
authors.affiliation: University of Antwerp, Antwerp, Belgium. pierre.vandamme@uantwerpen.be.
authors.forename: Pierre
authors.initials: P
authors.lastname: Van Damme
authors.affiliation: Genticel, Paris, France.
authors.forename: Myriam
authors.initials: M
authors.lastname: Bouillette-Marussig
authors.affiliation: University of Antwerp, Antwerp, Belgium.
authors.forename: Annick
authors.initials: A
authors.lastname: Hens
authors.affiliation: University of Antwerp, Antwerp, Belgium.
authors.forename: Ilse
authors.initials: I
authors.lastname: De Coster
authors.affiliation: Department of Molecular Diagnostics, AML, Sonic Healthcare, Antwerp, Belgium.
authors.forename: Christophe
authors.initials: C
authors.lastname: Depuydt
authors.affiliation: Tusk Therapeutics, Meise, Belgium.
authors.forename: Anne
authors.initials: A
authors.lastname: Goubier
authors.affiliation: University of Antwerp, Antwerp, Belgium.
authors.forename: Viggo
authors.initials: V
authors.lastname: Van Tendeloo
authors.affiliation: University of Antwerp, Antwerp, Belgium.
authors.forename: Nathalie
authors.initials: N
authors.lastname: Cools
authors.affiliation: University of Antwerp, Antwerp, Belgium.
authors.forename: Herman
authors.initials: H
authors.lastname: Goossens
authors.affiliation: Edmond de Rothschild Investment Partners, Paris, France.
authors.forename: Thierry
authors.initials: T
authors.lastname: Hercend
authors.affiliation: Genticel, Labège, France.
authors.forename: Benedikt
authors.initials: B
authors.lastname: Timmerman
authors.affiliation: Genticel, Paris, France.
authors.forename: Marie-Christine
authors.initials: MC
authors.lastname: Bissery
mesh_terms: D000276:Adjuvants, Immunologic / Q000627:therapeutic use*; D000293:Adolescent; D000328:Adult; D000634:Aminoquinolines / Q000627:therapeutic use*; D002584:Cervix Uteri / Q000166:cytology; D004268:DNA-Binding Proteins / Q000276:immunology*; D004311:Double-Blind Method; D005260:Female; D052162:Human papillomavirus 16 / Q000276:immunology*; D052161:Human papillomavirus 18 / Q000276:immunology*; D006801:Humans; D000077271:Imiquimod; D008875:Middle Aged; D009856:Oncogene Proteins, Viral / Q000276:immunology*; D050725:Papillomavirus E7 Proteins / Q000276:immunology*; D030361:Papillomavirus Infections / Q000821:virology; D053918:Papillomavirus Vaccines / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology; D002583:Uterine Cervical Neoplasms / Q000517:prevention & control* / Q000821:virology; D014611:Vaccination; D019562:Viral Load / Q000187:drug effects; D055815:Young Adult
chemical_list: D000276:Adjuvants, Immunologic; D000634:Aminoquinolines; D004268:DNA-Binding Proteins; C052633:E7 protein, Human papillomavirus type 18; D009856:Oncogene Proteins, Viral; D050725:Papillomavirus E7 Proteins; D053918:Papillomavirus Vaccines; C059731:oncogene protein E7, Human papillomavirus type 16; D000077271:Imiquimod