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Cancer Immunology, Immunotherapy

, Volume 53, Issue 7, pp 642–650 | Cite as

Phase I/II trial of immunogenicity of a human papillomavirus (HPV) type 16 E7 protein–based vaccine in women with oncogenic HPV-positive cervical intraepithelial neoplasia

  • Sophie HallezEmail author
  • Philippe Simon
  • Frédéric Maudoux
  • Jean Doyen
  • Jean-Christophe Noël
  • Aude Beliard
  • Xavier Capelle
  • Frédéric Buxant
  • Isabelle Fayt
  • Anne-Cécile Lagrost
  • Pascale Hubert
  • Colette Gerday
  • Arsène Burny
  • Jacques Boniver
  • Jean-Michel Foidart
  • Philippe Delvenne
  • Nathalie Jacobs
Original Article

Abstract

Purpose: Infection with oncogenic human papillomavirus (HPV) and HPV-16 in particular is a leading cause of anogenital neoplasia. High-grade intraepithelial lesions require treatment because of their potential to progress to invasive cancer. Numerous preclinical studies have demonstrated the therapeutic potential of E7-directed vaccination strategies in mice tumour models. In the present study, we tested the immunogenicity of a fusion protein (PD-E7) comprising a mutated HPV-16 E7 linked to the first 108 amino acids of Haemophilus influenzae protein D, formulated in the GlaxoSmithKline Biologicals adjuvant AS02B, in patients bearing oncogenic HPV-positive cervical intraepithelial neoplasia (CIN). Methods: Seven patients, five with a CIN3 and two with a CIN1, received three intramuscular injections of adjuvanted PD-E7 at 2-week intervals. Three additional CIN1 patients received a placebo. CIN3 patients underwent conization 8 weeks postvaccination. Cytokine flow cytometry and ELISA were used to monitor antigen-specific cellular and antibody responses from blood taken before and after vaccine or placebo injection. Results: Some patients had preexisting systemic IFN-γ CD4+ (1/10) and CD8+ (5/10) responses to PD-E7. Vaccination, not placebo injection, elicited systemic specific immune responses in the majority of the patients. Five vaccinated patients (71%) showed significantly increased IFN-γ CD8+ cell responses upon PD-E7 stimulation. Two responding patients generated long-term T-cell immunity toward the vaccine antigen and E7 as well as a weak H. influenzae protein D (PD)–directed CD4+ response. All the vaccinated patients, but not the placebo, made significant E7- and PD-specific IgG. Conclusions: The encouraging results obtained from this study performed on a limited number of subjects justify further analysis of the efficacy of the PD-E7/AS02B vaccine in CIN patients.

Keywords

CD4 CD8 Human papillomavirus IFN-γ Immunotherapy 

Notes

Acknowledgements

We thank GlaxoSmithKline Biologicals, Belgium, for providing the study vaccine. Sonia Pisvin and Renee Gathy provided excellent technical assistance. P.D. and N.J. are supported by the Belgian National Fund for Scientific Research. This work was supported by the Yvonne Boël Foundation, the Belgian National Fund for Scientific Research and the Region Wallonne.

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Copyright information

© Springer-Verlag 2004

Authors and Affiliations

  • Sophie Hallez
    • 1
    Email author
  • Philippe Simon
    • 2
  • Frédéric Maudoux
    • 1
  • Jean Doyen
    • 4
  • Jean-Christophe Noël
    • 3
  • Aude Beliard
    • 4
  • Xavier Capelle
    • 4
  • Frédéric Buxant
    • 2
  • Isabelle Fayt
    • 3
  • Anne-Cécile Lagrost
    • 5
  • Pascale Hubert
    • 5
  • Colette Gerday
    • 4
  • Arsène Burny
    • 1
  • Jacques Boniver
    • 5
  • Jean-Michel Foidart
    • 4
  • Philippe Delvenne
    • 5
  • Nathalie Jacobs
    • 5
  1. 1.Chimie Biologique, Institut de Biologie et de Médecine MoléculairesUniversité Libre de BruxellesGosseliesBelgium
  2. 2.Department of Obstetrics and GynaecologyHôpital ErasmeBrusselsBelgium
  3. 3.Department of Clinical PathologyHôpital ErasmeBrusselsBelgium
  4. 4.Department of GynecologyUniversity of LiègeLiègeBelgium
  5. 5.Department of Pathology, CRCEUniversity of LiègeLiègeBelgium

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