Gene Therapy against Murine Melanoma B16F10-Nex2 Using IL-13R alpha 2-Fc Chimera and Interleukin 12 in Association with a Cyclopalladated Drug
Autor(a) principal: | |
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Data de Publicação: | 2008 |
Outros Autores: | , , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Institucional da UNIFESP |
Texto Completo: | http://repositorio.unifesp.br/handle/11600/30871 http://dx.doi.org/10.1593/tlo.08115 |
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. |
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Hebeler-Barbosa, Flavia [UNIFESP]Rodrigues, Elaine Guadalupe [UNIFESP]Puccia, Rosana [UNIFESP]Caires, Antonio Carlos FaveroTravassos, Luiz Rodolpho [UNIFESP]Universidade Federal de São Paulo (UNIFESP)Univ Mogi das Cruzes2016-01-24T13:51:39Z2016-01-24T13:51:39Z2008-09-01Translational Oncology. Ann Arbor: Neoplasia Press, v. 1, n. 3, p. 110-120, 2008.1936-5233http://repositorio.unifesp.br/handle/11600/30871http://dx.doi.org/10.1593/tlo.0811510.1593/tlo.08115WOS:000272467200001Interleukin 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.Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Brazilian National Research CouncilUniversidade Federal de São Paulo, Dept Microbiol Imunol & Parasitol, UNONEX, BR-04023062 São Paulo, BrazilUniversidade Federal de São Paulo, Dept Microbiol Imunol & Parasitol, Disciplina Biol Celular, BR-04023062 São Paulo, BrazilUniv Mogi das Cruzes, São Paulo, BrazilUniversidade Federal de São Paulo, Dept Microbiol Imunol & Parasitol, UNONEX, BR-04023062 São Paulo, BrazilUniversidade Federal de São Paulo, Dept Microbiol Imunol & Parasitol, Disciplina Biol Celular, BR-04023062 São Paulo, BrazilWeb of Science110-120engNeoplasia PressTranslational OncologyGene Therapy against Murine Melanoma B16F10-Nex2 Using IL-13R alpha 2-Fc Chimera and Interleukin 12 in Association with a Cyclopalladated Druginfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleinfo:eu-repo/semantics/openAccessreponame:Repositório Institucional da UNIFESPinstname:Universidade Federal de São Paulo (UNIFESP)instacron:UNIFESP11600/308712022-09-27 12:00:37.209metadata only accessoai:repositorio.unifesp.br:11600/30871Repositório InstitucionalPUBhttp://www.repositorio.unifesp.br/oai/requestopendoar:34652022-09-27T15:00:37Repositório Institucional da UNIFESP - Universidade Federal de São Paulo (UNIFESP)false |
dc.title.en.fl_str_mv |
Gene Therapy against Murine Melanoma B16F10-Nex2 Using IL-13R alpha 2-Fc Chimera and Interleukin 12 in Association with a Cyclopalladated Drug |
title |
Gene Therapy against Murine Melanoma B16F10-Nex2 Using IL-13R alpha 2-Fc Chimera and Interleukin 12 in Association with a Cyclopalladated Drug |
spellingShingle |
Gene Therapy against Murine Melanoma B16F10-Nex2 Using IL-13R alpha 2-Fc Chimera and Interleukin 12 in Association with a Cyclopalladated Drug Hebeler-Barbosa, Flavia [UNIFESP] |
title_short |
Gene Therapy against Murine Melanoma B16F10-Nex2 Using IL-13R alpha 2-Fc Chimera and Interleukin 12 in Association with a Cyclopalladated Drug |
title_full |
Gene Therapy against Murine Melanoma B16F10-Nex2 Using IL-13R alpha 2-Fc Chimera and Interleukin 12 in Association with a Cyclopalladated Drug |
title_fullStr |
Gene Therapy against Murine Melanoma B16F10-Nex2 Using IL-13R alpha 2-Fc Chimera and Interleukin 12 in Association with a Cyclopalladated Drug |
title_full_unstemmed |
Gene Therapy against Murine Melanoma B16F10-Nex2 Using IL-13R alpha 2-Fc Chimera and Interleukin 12 in Association with a Cyclopalladated Drug |
title_sort |
Gene Therapy against Murine Melanoma B16F10-Nex2 Using IL-13R alpha 2-Fc Chimera and Interleukin 12 in Association with a Cyclopalladated Drug |
author |
Hebeler-Barbosa, Flavia [UNIFESP] |
author_facet |
Hebeler-Barbosa, Flavia [UNIFESP] Rodrigues, Elaine Guadalupe [UNIFESP] Puccia, Rosana [UNIFESP] Caires, Antonio Carlos Favero Travassos, Luiz Rodolpho [UNIFESP] |
author_role |
author |
author2 |
Rodrigues, Elaine Guadalupe [UNIFESP] Puccia, Rosana [UNIFESP] Caires, Antonio Carlos Favero Travassos, Luiz Rodolpho [UNIFESP] |
author2_role |
author author author author |
dc.contributor.institution.none.fl_str_mv |
Universidade Federal de São Paulo (UNIFESP) Univ Mogi das Cruzes |
dc.contributor.author.fl_str_mv |
Hebeler-Barbosa, Flavia [UNIFESP] Rodrigues, Elaine Guadalupe [UNIFESP] Puccia, Rosana [UNIFESP] Caires, Antonio Carlos Favero Travassos, Luiz Rodolpho [UNIFESP] |
description |
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. |
publishDate |
2008 |
dc.date.issued.fl_str_mv |
2008-09-01 |
dc.date.accessioned.fl_str_mv |
2016-01-24T13:51:39Z |
dc.date.available.fl_str_mv |
2016-01-24T13:51:39Z |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/article |
format |
article |
status_str |
publishedVersion |
dc.identifier.citation.fl_str_mv |
Translational Oncology. Ann Arbor: Neoplasia Press, v. 1, n. 3, p. 110-120, 2008. |
dc.identifier.uri.fl_str_mv |
http://repositorio.unifesp.br/handle/11600/30871 http://dx.doi.org/10.1593/tlo.08115 |
dc.identifier.issn.none.fl_str_mv |
1936-5233 |
dc.identifier.doi.none.fl_str_mv |
10.1593/tlo.08115 |
dc.identifier.wos.none.fl_str_mv |
WOS:000272467200001 |
identifier_str_mv |
Translational Oncology. Ann Arbor: Neoplasia Press, v. 1, n. 3, p. 110-120, 2008. 1936-5233 10.1593/tlo.08115 WOS:000272467200001 |
url |
http://repositorio.unifesp.br/handle/11600/30871 http://dx.doi.org/10.1593/tlo.08115 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.ispartof.none.fl_str_mv |
Translational Oncology |
dc.rights.driver.fl_str_mv |
info:eu-repo/semantics/openAccess |
eu_rights_str_mv |
openAccess |
dc.format.none.fl_str_mv |
110-120 |
dc.publisher.none.fl_str_mv |
Neoplasia Press |
publisher.none.fl_str_mv |
Neoplasia Press |
dc.source.none.fl_str_mv |
reponame:Repositório Institucional da UNIFESP instname:Universidade Federal de São Paulo (UNIFESP) instacron:UNIFESP |
instname_str |
Universidade Federal de São Paulo (UNIFESP) |
instacron_str |
UNIFESP |
institution |
UNIFESP |
reponame_str |
Repositório Institucional da UNIFESP |
collection |
Repositório Institucional da UNIFESP |
repository.name.fl_str_mv |
Repositório Institucional da UNIFESP - Universidade Federal de São Paulo (UNIFESP) |
repository.mail.fl_str_mv |
|
_version_ |
1802764173261668352 |