Advantage of a new intra-cheek immunization route for therapeutic vaccines of human papillomavirus-associated head and neck cancers.
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1
UPMC Paris 06, CNRS 7211/INSERM 959, Groupe hospitalier Pitié-Salpêtrière, France
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2
Université Denis Diderot Paris 07, France
Papillomavirus (HPV)-16 infection has been recently associated with oropharyngeal head and neck cancers (HNCs) that express the viral E6 and E7 oncoproteins. The licensed vaccines are efficient for the prevention of HPV infection, but not for established tumors. Therefore innovative therapeutic vaccines targeting HPV oncogenes are required. Recently, we have described the efficiency of therapeutic intra-dermic DNA vaccinations using plasmo-virus like particles carrying the E7 oncoprotein (pVLPs-E7) associated with electroporation to control the growth of TC1 tumors subcutaneously injected in the flank of C57Bl6 mice. The present study aims at comparing immune and anti-tumoral efficacy of different routes of vaccination with pVLPs-E7.
Here, we have used an orthotopic model of HPV-induced HNCs where TC1 cells were injected into the cheek of C57BL6 mice. Tumor growth and anti-E7 immune response were compared after intra-cheek (i.c.) or intra-dermal (i.d.) pVLP-E7 vaccinations. While i.d. route gave rise to better systemic anti-E7 cellular immune response than i.c. route, both routes elicited superposable local anti-E7 immune responses. Interestingly, only i.c. route elicited an anti-E7 humoral response. When vaccinations were performed in mice bearing well-established tumors, a better therapeutic effect was observed using i.c immunizations. Furthermore, anti-tumoral responses were optimized by combining vaccinations with TLR agonists (Imiquimod and CpG) as adjuvants.
Our data show that i.c. mucosal vaccinations with pVLP-E7 combined with adjuvants, evaluated in an orthotopic tumor model, appear to be a valuable therapeutic strategy for HPV-induced HNCs.
Keywords:
mucosal immunization,
head and neck cancer,
DNA vaccine,
Orthotopic model,
TLR agonists
Conference:
15th International Congress of Immunology (ICI), Milan, Italy, 22 Aug - 27 Aug, 2013.
Presentation Type:
Abstract
Topic:
Translational immunology and immune intervention
Citation:
Macedo
R,
Lescaille
G,
Mateo
V,
Baillou
C,
Bellier
B and
Lemoine
F
(2013). Advantage of a new intra-cheek immunization route for therapeutic vaccines of human papillomavirus-associated head and neck cancers..
Front. Immunol.
Conference Abstract:
15th International Congress of Immunology (ICI).
doi: 10.3389/conf.fimmu.2013.02.00033
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Received:
08 Mar 2013;
Published Online:
22 Aug 2013.
*
Correspondence:
Mr. Rodney Macedo, UPMC Paris 06, CNRS 7211/INSERM 959, Groupe hospitalier Pitié-Salpêtrière, Paris, France, rodney_macedo@hotmail.com