Article (Scientific journals)
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
Hallez, Sophie; Simon, Philippe; Maudoux, Frédéric et al.
2004In Cancer Immunology, Immunotherapy, 53 (7), p. 642-650
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Keywords :
CD4; CD8; human papillomavirus; IFN-gamma; immunotherapy
Abstract :
[en] 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-gamma 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-gamma 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.
Disciplines :
Immunology & infectious disease
Oncology
Author, co-author :
Hallez, Sophie
Simon, Philippe;  Department of Obstetrics and Gynaecology, Hopital Erasme,
Maudoux, Frédéric
Doyen, Jean ;  Centre Hospitalier Universitaire de Liège - CHU > Gynécologie-Obstétrique CHR
Noël, Jean-Christophe
Beliard, Aude ;  Centre Hospitalier Universitaire de Liège - CHU > Gynécologie-Obstétrique CHR
Capelle, Xavier ;  Centre Hospitalier Universitaire de Liège - CHU > Gynécologie-Obstétrique
Buxant, Frédéric
Fayt, Isabelle
Lagrost, Anne-Cécile
Hubert, Pascale  ;  Université de Liège - ULiège > Département des sciences biomédicales et précliniques > Anatomie et cytologie pathologiques
Gerday, Colette ;  Centre Hospitalier Universitaire de Liège - CHU > Gynécologie-Obstétrique CHR
Burny, Arsène ;  Université de Liège - ULiège > Agro Biotech Gembloux
Boniver, Jacques ;  Université de Liège - ULiège > Département des sciences biomédicales et précliniques > Anatomie et cytologie pathologiques
Foidart, Jean-Michel ;  Université de Liège - ULiège > Département des sciences cliniques > Gynécologie - Obstétrique
Delvenne, Philippe ;  Université de Liège - ULiège > Département des sciences biomédicales et précliniques > Anatomie et cytologie pathologiques
Jacobs, Nathalie  ;  Université de Liège - ULiège > Département des sciences biomédicales et précliniques > Anatomie et cytologie pathologiques
More authors (7 more) Less
Language :
English
Title :
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
Publication date :
July 2004
Journal title :
Cancer Immunology, Immunotherapy
ISSN :
0340-7004
eISSN :
1432-0851
Publisher :
Springer Verlag, New York, United States - New York
Volume :
53
Issue :
7
Pages :
642-650
Peer reviewed :
Peer Reviewed verified by ORBi
Funders :
F.R.S.-FNRS - Fonds de la Recherche Scientifique [BE]
DGTRE - Région wallonne. Direction générale des Technologies, de la Recherche et de l'Énergie [BE]
Fonds Yvonne Boël [BE]
Commentary :
The original publication is available at www.springerlink.com
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since 30 January 2009

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