Unpublished conference/Abstract (Scientific congresses and symposiums)
Phase I/IIclinical trial of local GM-CSF application in patients with cervical HPV-associated low grade squamous intraepithelial lesions
Hubert, Pascale; Doyen, Jean; Chapelle, X. et al.
200724th International Papillomavirus Conference and Clinical Workshops
 

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Abstract :
[en] Background: Quantitative and functional alterations of professional antigen-presenting cells (APC) in SIL suggest that these lesions may have a diminished capacity to capture viral antigens. Moreover, GM-CSF (whose production is decreased in HPV-transformed keratinocytes) is an essential factor for the migration of APC in cervical (pre)neoplastic lesions formed in vitro and transplanted in vivo on mouse. In this study we performed a phase I/II clinical trial in order to determine whether a local application of GM-CSF on cervical low-grade squamous intraepithelial lesions (LSIL) might increase the recruitment of APC into the epithelium and indirectly the viral antigen presentation to the immune system. Methods: Fifteen patients with LSIL (10 GM-CSF and 5 placebo) were enrolled in this study. Patients received 4 GM-CSF applications (or placebo gel) and were followed during 6-7 months. APC infiltration was quantified by immunostaining with anti-CD1a mAb. Cellular immune response was evaluated by using an IFN-gamma intracellular staining on PBMC stimulated in vitro with the E7 HPV16 protein and L1 HPV16 Virus-like particles (VLP). Hybrid capture was performed to semi-quantify the viral DNA in cervical brush specimens. Results: GM-CSF applications were well tolerated in all patients. No difference in the cytological/histological and viral parameters assessed at 2 and 6 months after the last application was observed between the GM-CSF and the placebo group. An increased number of CD1a+ APC was observed in 6/10 patients treated by GM-CSF compared to 1/5 patient in the placebo group. There was an increased immune response against HPV in the GM-CSF group showed by NK and T cells producing IFN-gamma.
Disciplines :
Reproductive medicine (gynecology, andrology, obstetrics)
Author, co-author :
Hubert, Pascale  ;  Université de Liège - ULiège > Département des sciences biomédicales et précliniques > Anatomie et cytologie pathologiques
Doyen, Jean ;  Université de Liège - ULiège > Gynécologie-Obstétrique CHR
Chapelle, X.
Evrard, Brigitte  ;  Université de Liège - ULiège > Département de pharmacie > Pharmacie galénique
Gerday, Colette ;  Université de Liège - ULiège > Gynécologie-Obstétrique CHR
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 - Labo de biologie des tumeurs et du développement
Jacobs, Nathalie  ;  Université de Liège - ULiège > Département des sciences biomédicales et précliniques > Anatomie et cytologie pathologiques
Language :
English
Title :
Phase I/IIclinical trial of local GM-CSF application in patients with cervical HPV-associated low grade squamous intraepithelial lesions
Publication date :
2007
Event name :
24th International Papillomavirus Conference and Clinical Workshops
Event place :
Bejing, China
Event date :
3-7 novembre 2007
Audience :
International
Funders :
DGRE - Région wallonne. Direction générale des Relations extérieures [BE]
F.R.S.-FNRS - Fonds de la Recherche Scientifique [BE]
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since 25 August 2010

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