Semliki forest virus vectors engineered to express higher IL-12 levels induce efficient elimination of murine colon adenocarcinomas

To evaluate the use of alphavirus vectors for tumor treatment we have constructed and compared two Semliki Forest virus (SFV) vectors expressing different levels of IL-12. SFV-IL-12 expresses both IL-12 subunits from a single subgenomic promoter, while in SFV-enhIL-12 each IL-12 subunit is expressed...

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Autores: Rodriguez-Madoz, J.R. (Juan Roberto)|||/items/9c21019b-aeba-4cdc-b78e-178a176da535, Prieto, J. (Jesús)|||/items/0d9c3dec-4a09-400d-8c83-23ece1096c71, Smerdou-Picazo, C. (Cristian)|||/items/48fd1bd4-6483-45c9-9951-8a1b04873227
Formato: artículo
Fecha de publicación:2005
País:España
Recursos:Universidad de Navarra
Repositorio:Dadun. Depósito Académico Digital de la Universidad de Navarra
Idioma:inglés
OAI Identifier:oai:dadun.unav.edu:10171/23177
Acesso em linha:https://hdl.handle.net/10171/23177
Access Level:acceso abierto
Palavra-chave:Semliki Forest virus vectors
SFV translation enhancer
Gene therapy
MC38
Colon adenocarcinoma
IL-12
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spelling Semliki forest virus vectors engineered to express higher IL-12 levels induce efficient elimination of murine colon adenocarcinomasRodriguez-Madoz, J.R. (Juan Roberto)|||/items/9c21019b-aeba-4cdc-b78e-178a176da535Prieto, J. (Jesús)|||/items/0d9c3dec-4a09-400d-8c83-23ece1096c71Smerdou-Picazo, C. (Cristian)|||/items/48fd1bd4-6483-45c9-9951-8a1b04873227Semliki Forest virus vectorsSFV translation enhancerGene therapyMC38Colon adenocarcinomaIL-12To evaluate the use of alphavirus vectors for tumor treatment we have constructed and compared two Semliki Forest virus (SFV) vectors expressing different levels of IL-12. SFV-IL-12 expresses both IL-12 subunits from a single subgenomic promoter, while in SFV-enhIL-12 each IL-12 subunit is expressed from an independent subgenomic promoter fused to the SFV capsid translation enhancer. This latter strategy provided an eightfold increase of IL-12 expression. We chose the poorly immunogenic MC38 colon adenocarcinoma model to evaluate the therapeutic potential of SFV vectors. A single intratumoral injection of 10(8) viral particles of SFV-IL-12 or SFV-enh-IL-12 induced>or=80% complete tumor regressions with long-term tumor-free survival. However, lower doses of SFV-enhIL-12 were more efficient than SFV-IL-12 in inducing antitumoral responses, indicating a positive correlation between the IL-12 expression level and the therapeutic effect. Moreover, repeated intratumoral injections of suboptimal doses of SFV-enhIL-12 increased the antitumoral response. In all cases SFV vectors were more efficient at eliminating tumors than a first-generation adenovirus vector expressing IL-12. In addition, the antitumoral effect of SFV vectors was only moderately affected by preimmunization of animals with high doses of SFV vectors. This antitumoral effect was produced, at least partially, by a potent CTL-mediated immune response.NatureDadun. Depósito Académico Digital Universidad de Navarra20122012-09-2520052005-01-0120052005-01-01journal articlehttp://purl.org/coar/resource_type/c_6501info:eu-repo/semantics/articleapplication/pdfhttps://hdl.handle.net/10171/23177reponame:Dadun. Depósito Académico Digital de la Universidad de Navarrainstname:Universidad de NavarraInglésengopen accesshttp://purl.org/coar/access_right/c_abf2info:eu-repo/semantics/openAccessoai:dadun.unav.edu:10171/231772026-06-21T12:47:57Z
dc.title.none.fl_str_mv Semliki forest virus vectors engineered to express higher IL-12 levels induce efficient elimination of murine colon adenocarcinomas
title Semliki forest virus vectors engineered to express higher IL-12 levels induce efficient elimination of murine colon adenocarcinomas
spellingShingle Semliki forest virus vectors engineered to express higher IL-12 levels induce efficient elimination of murine colon adenocarcinomas
Rodriguez-Madoz, J.R. (Juan Roberto)|||/items/9c21019b-aeba-4cdc-b78e-178a176da535
Semliki Forest virus vectors
SFV translation enhancer
Gene therapy
MC38
Colon adenocarcinoma
IL-12
title_short Semliki forest virus vectors engineered to express higher IL-12 levels induce efficient elimination of murine colon adenocarcinomas
title_full Semliki forest virus vectors engineered to express higher IL-12 levels induce efficient elimination of murine colon adenocarcinomas
title_fullStr Semliki forest virus vectors engineered to express higher IL-12 levels induce efficient elimination of murine colon adenocarcinomas
title_full_unstemmed Semliki forest virus vectors engineered to express higher IL-12 levels induce efficient elimination of murine colon adenocarcinomas
title_sort Semliki forest virus vectors engineered to express higher IL-12 levels induce efficient elimination of murine colon adenocarcinomas
dc.creator.none.fl_str_mv Rodriguez-Madoz, J.R. (Juan Roberto)|||/items/9c21019b-aeba-4cdc-b78e-178a176da535
Prieto, J. (Jesús)|||/items/0d9c3dec-4a09-400d-8c83-23ece1096c71
Smerdou-Picazo, C. (Cristian)|||/items/48fd1bd4-6483-45c9-9951-8a1b04873227
author Rodriguez-Madoz, J.R. (Juan Roberto)|||/items/9c21019b-aeba-4cdc-b78e-178a176da535
author_facet Rodriguez-Madoz, J.R. (Juan Roberto)|||/items/9c21019b-aeba-4cdc-b78e-178a176da535
Prieto, J. (Jesús)|||/items/0d9c3dec-4a09-400d-8c83-23ece1096c71
Smerdou-Picazo, C. (Cristian)|||/items/48fd1bd4-6483-45c9-9951-8a1b04873227
author_role author
author2 Prieto, J. (Jesús)|||/items/0d9c3dec-4a09-400d-8c83-23ece1096c71
Smerdou-Picazo, C. (Cristian)|||/items/48fd1bd4-6483-45c9-9951-8a1b04873227
author2_role author
author
dc.contributor.none.fl_str_mv Dadun. Depósito Académico Digital Universidad de Navarra
dc.subject.none.fl_str_mv Semliki Forest virus vectors
SFV translation enhancer
Gene therapy
MC38
Colon adenocarcinoma
IL-12
topic Semliki Forest virus vectors
SFV translation enhancer
Gene therapy
MC38
Colon adenocarcinoma
IL-12
description To evaluate the use of alphavirus vectors for tumor treatment we have constructed and compared two Semliki Forest virus (SFV) vectors expressing different levels of IL-12. SFV-IL-12 expresses both IL-12 subunits from a single subgenomic promoter, while in SFV-enhIL-12 each IL-12 subunit is expressed from an independent subgenomic promoter fused to the SFV capsid translation enhancer. This latter strategy provided an eightfold increase of IL-12 expression. We chose the poorly immunogenic MC38 colon adenocarcinoma model to evaluate the therapeutic potential of SFV vectors. A single intratumoral injection of 10(8) viral particles of SFV-IL-12 or SFV-enh-IL-12 induced>or=80% complete tumor regressions with long-term tumor-free survival. However, lower doses of SFV-enhIL-12 were more efficient than SFV-IL-12 in inducing antitumoral responses, indicating a positive correlation between the IL-12 expression level and the therapeutic effect. Moreover, repeated intratumoral injections of suboptimal doses of SFV-enhIL-12 increased the antitumoral response. In all cases SFV vectors were more efficient at eliminating tumors than a first-generation adenovirus vector expressing IL-12. In addition, the antitumoral effect of SFV vectors was only moderately affected by preimmunization of animals with high doses of SFV vectors. This antitumoral effect was produced, at least partially, by a potent CTL-mediated immune response.
publishDate 2005
dc.date.none.fl_str_mv 2005
2005-01-01
2005
2005-01-01
2012
2012-09-25
dc.type.none.fl_str_mv journal article
http://purl.org/coar/resource_type/c_6501
dc.type.openaire.fl_str_mv info:eu-repo/semantics/article
format article
dc.identifier.none.fl_str_mv https://hdl.handle.net/10171/23177
url https://hdl.handle.net/10171/23177
dc.language.none.fl_str_mv Inglés
eng
language_invalid_str_mv Inglés
language eng
dc.rights.none.fl_str_mv open access
http://purl.org/coar/access_right/c_abf2
dc.rights.openaire.fl_str_mv info:eu-repo/semantics/openAccess
rights_invalid_str_mv open access
http://purl.org/coar/access_right/c_abf2
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv Nature
publisher.none.fl_str_mv Nature
dc.source.none.fl_str_mv reponame:Dadun. Depósito Académico Digital de la Universidad de Navarra
instname:Universidad de Navarra
instname_str Universidad de Navarra
reponame_str Dadun. Depósito Académico Digital de la Universidad de Navarra
collection Dadun. Depósito Académico Digital de la Universidad de Navarra
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15,300719

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