Gene Therapy against Murine Melanoma B16F10-Nex2 Using IL-13R alpha 2-Fc Chimera and Interleukin 12 in Association with a Cyclopalladated Drug

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dc.contributor.author Hebeler-Barbosa, Flavia [UNIFESP]
dc.contributor.author Rodrigues, Elaine Guadalupe [UNIFESP]
dc.contributor.author Puccia, Rosana [UNIFESP]
dc.contributor.author Caires, Antonio Carlos Favero
dc.contributor.author Travassos, Luiz Rodolpho [UNIFESP]
dc.date.accessioned 2016-01-24T13:51:39Z
dc.date.available 2016-01-24T13:51:39Z
dc.date.issued 2008-09-01
dc.identifier http://dx.doi.org/10.1593/tlo.08115
dc.identifier.citation Translational Oncology. Ann Arbor: Neoplasia Press, v. 1, n. 3, p. 110-120, 2008.
dc.identifier.issn 1936-5233
dc.identifier.uri http://repositorio.unifesp.br/handle/11600/30871
dc.description.abstract Interleukin 13 (IL-13) is immunoregulatory in many diseases, including cancer. the protective or suppressive role of CD1-restricted natural killer T cells (NKT cells) in tumor immunosurveillance and immunity is well documented. Interleukin 12 (IL-12) can activate type I NKT cells to produce interferon-gamma (IFN-gamma), whereas type II NKT cells may produce IL-13. the high-affinity chain of IL-13R alpha 2 may act as negative inhibitor, suppressing the action of IL-13 and helping to maintain tumor immunosurveillance. We constructed an mIL-13R alpha 2-Fc chimera in a eukaryotic expression vector and confirmed the identity of the recombinant protein by immunoblot analysis and binding to IL-13 in chemiluminescent ELISA. Such DNA vaccine was tested against syngeneic B16F10-Nex2 murine melanoma. in vivo experiments showed a protective effect mediated by high production of IFN-gamma and down-regulation of anti-inflammatory interleukins mainly by NKT 1.1(+) T cells. Biochemoterapy in vivo with plasmid encoding mIL-13R alpha 2-Fc in association with plasmid encoding IL-12 and the 7A cyclopalladated drug led to a significant reduction in the tumor evolution with 30% tumor-free mice. We conclude that IL-12 gene therapy, followed by continuous administration of IL-13R alpha 2-Fc gene along with 7A-drug has antitumor activity involving the high production of proinflammatory cytokines and low immune suppression, specifically by NK1.1(+) T cells producing IL-13 and IL-10. en
dc.description.sponsorship Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)
dc.description.sponsorship Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
dc.description.sponsorship Brazilian National Research Council
dc.format.extent 110-120
dc.language.iso eng
dc.publisher Neoplasia Press
dc.relation.ispartof Translational Oncology
dc.rights Acesso aberto
dc.title Gene Therapy against Murine Melanoma B16F10-Nex2 Using IL-13R alpha 2-Fc Chimera and Interleukin 12 in Association with a Cyclopalladated Drug en
dc.type Artigo
dc.contributor.institution Universidade Federal de São Paulo (UNIFESP)
dc.contributor.institution Univ Mogi das Cruzes
dc.description.affiliation Universidade Federal de São Paulo, Dept Microbiol Imunol & Parasitol, UNONEX, BR-04023062 São Paulo, Brazil
dc.description.affiliation Universidade Federal de São Paulo, Dept Microbiol Imunol & Parasitol, Disciplina Biol Celular, BR-04023062 São Paulo, Brazil
dc.description.affiliation Univ Mogi das Cruzes, São Paulo, Brazil
dc.description.affiliationUnifesp Universidade Federal de São Paulo, Dept Microbiol Imunol & Parasitol, UNONEX, BR-04023062 São Paulo, Brazil
dc.description.affiliationUnifesp Universidade Federal de São Paulo, Dept Microbiol Imunol & Parasitol, Disciplina Biol Celular, BR-04023062 São Paulo, Brazil
dc.identifier.doi 10.1593/tlo.08115
dc.description.source Web of Science
dc.identifier.wos WOS:000272467200001



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