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

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

Autor Hebeler-Barbosa, Flavia Autor UNIFESP Google Scholar
Rodrigues, Elaine Guadalupe Autor UNIFESP Google Scholar
Puccia, Rosana Autor UNIFESP Google Scholar
Caires, Antonio Carlos Favero Google Scholar
Travassos, Luiz Rodolpho Autor UNIFESP Google Scholar
Instituição Universidade Federal de São Paulo (UNIFESP)
Univ Mogi das Cruzes
Resumo 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.
Idioma Inglês
Financiador Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)
Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
Brazilian National Research Council
Data de publicação 2008-09-01
Publicado em Translational Oncology. Ann Arbor: Neoplasia Press, v. 1, n. 3, p. 110-120, 2008.
ISSN 1936-5233 (Sherpa/Romeo, fator de impacto)
Publicador Neoplasia Press
Extensão 110-120
Fonte http://dx.doi.org/10.1593/tlo.08115
Direito de acesso Acesso aberto Open Access
Tipo Artigo
Web of Science WOS:000272467200001
Endereço permanente http://repositorio.unifesp.br/handle/11600/30871

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