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Combination of intratumoral injections of vaccinia virus MVA expressing GM-CSF and immunization with DNA vaccine prolongs the survival of mice bearing HPV16 induced tumors with downregulated expression of MHC class I molecules
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SYSNO ASEP 0092902 Document Type J - Journal Article R&D Document Type Journal Article Subsidiary J Ostatní články Title Combination of intratumoral injections of vaccinia virus MVA expressing GM-CSF and immunization with DNA vaccine prolongs the survival of mice bearing HPV16 induced tumors with downregulated expression of MHC class I molecules Title Kombinace intratumorálního podání vakcinia viru MVA exprimujícího GM-CSF a imunizace DNA vakcínou prodlužuje přežití myší nesoucích HPV16 indukované nádory se sníženou expresí MHC molekul I. třídy Author(s) Němečková, Š. (CZ)
Šmahel, M. (CZ)
Hainz, P. (CZ)
Macková, J. (CZ)
Zurková, K. (CZ)
Gabriel, P. (CZ)
Indrová, Marie (UMG-J) RID
Kutinová, L. (CZ)Source Title Neoplasma - ISSN 0028-2685
Roč. 54, č. 4 (2007), s. 326-333Number of pages 8 s. Language eng - English Country SK - Slovakia Keywords vaccinia virus MVA expressing GM-CSF ; DNA vaccine ; HPV16 induced tumors Subject RIV EB - Genetics ; Molecular Biology R&D Projects NR8004 GA MZd - Ministry of Health (MZ) CEZ AV0Z50520514 - UMG-J (2005-2011) Annotation The C57BL/6 mice bearing TC-1/A9 tumours exprimed HPV16 oncogenes and downregulated of H-2b molecules were immunized with highly immunogenic E7GGG.GUS DNA vaccine expressing the fused gene of modified HPV16 E7 (E7GGG) with E.coli β-glucuronidase (GUS). The tumors in situ were injected with recombinant vaccinia virus MVA expressing the gene for murine GM-CSF (MVA-GM-CSF). Two doses of the DNA vaccine combined with a local treatment with MVA-GM-CSF were able to inhibit significantly the growth of tumors. ELISPOT-IFNγ showed that in situ expression of the GM-CSF gene did not enhance the E7 specific systemic cell response. The local injections of MVA-GM-CSF induced an increase of intratumoral CD3+ T cell counts and the DNA vaccination resulted in up-regulation of MHC type I molecules on tumor cells in vivo. We suppose that i.t. delivery of MVA-GM-CSF changed the local tumor microenvironment and rendered tumors more attractive and better accessible to effector T cells. Workplace Institute of Molecular Genetics Contact Nikol Škňouřilová, nikol.sknourilova@img.cas.cz, Tel.: 241 063 217 Year of Publishing 2008
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