ORBi: Hallez Sophie - 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

Reference : Phase I/II trial of immunogenicity of a human papillomavirus (HPV) type 16 E7 protein-ba...


	Document type :	Scientific journals : Article
	Discipline(s) :	Human health sciences : Oncology Human health sciences : Immunology & infectious disease
	To cite this reference:	http://hdl.handle.net/2268/5212

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
Language :	English
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 - ULg > Département des sciences biomédicales et précliniques > Anatomie et cytologie pathologiques >]
	Gerday, Colette [Centre Hospitalier Universitaire de Liège - CHU > > Gynécologie-Obstétrique CHR >]
	Burny, Arsène [> > > >]
	Boniver, Jacques [Université de Liège - ULg > Département des sciences biomédicales et précliniques > Anatomie et cytologie pathologiques]
	Foidart, Jean-Michel [Université de Liège - ULg > Département des sciences cliniques > Gynécologie - Obstétrique >]
	Delvenne, Philippe [Université de Liège - ULg > Département des sciences biomédicales et précliniques > Anatomie et cytologie pathologiques >]
	Jacobs, Nathalie [Université de Liège - ULg > Département des sciences biomédicales et précliniques > Anatomie et cytologie pathologiques >]
Publication date :	Jul-2004
Journal title :	Cancer Immunology, Immunotherapy
Publisher :	Springer Verlag
Volume :	53
Issue/season :	7
Pages :	642-650
Peer reviewed :	Yes (verified by ORBi)
Audience :	International
ISSN :	0340-7004
City :	New York
Keywords :	[en] 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.
Funders :	Fonds de la Recherche Scientifique (Communauté française de Belgique) - F.R.S.-FNRS ; Région wallonne : Direction générale des Technologies, de la Recherche et de l'Energie - DGTRE ; Yvonne Boel Foundation
Target :	Researchers ; Professionals ; Students
Permalink :	http://hdl.handle.net/2268/5212
Other URL :	http://www.springerlink.com/content/e9ttuu985wh9xh9b/
Commentary :	The original publication is available at www.springerlink.com

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