A tumor-stroma targeted oncolytic adenovirus replicated in human ovary cancer samples and inhibited growth of disseminated solid tumors in mice

Autores
Lopez, Maria Veronica; Rivera, Angel A.; Viale, Diego Luis; Benedetti, Lorena Gabriela; Cuneo, Nicasio; Kimball, Kristopher J.; Wang, Minghui; Douglas, Joanne T.; Zhu, Zeng B.; Bravo, Alicia I.; Gidekel, Manuel; Alvarez, Ronald D.; Curiel, David T.; Podhajcer, Osvaldo Luis
Año de publicación
2012
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Targeting the tumor stroma in addition to the malignant cell compartment is of paramount importance to achieve complete tumor regression. In this work, we modified a previously designed tumor stroma-targeted conditionally replicative adenovirus (CRAd) based on the SPARC promoter by introducing a mutated E1A unable to bind pRB and pseudotyped with a chimeric Ad5/3 fiber (Ad F512v1), and assessed its replication/lytic capacity in ovary cancer in vitro and in vivo. AdF512v1 was able to replicate in fresh samples obtained from patients: (i) with primary human ovary cancer; (ii) that underwent neoadjuvant treatment; (iii) with metastatic disease. In addition, we show that four intraperitoneal (i.p.) injections of 5 × 10(10) v.p. eliminated 50% of xenografted human ovary tumors disseminated in nude mice. Moreover, AdF512v1 replication in tumor models was enhanced 15-40-fold when the tumor contained a mix of malignant and SPARC-expressing stromal cells (fibroblasts and endothelial cells). Contrary to the wild-type virus, AdF512v1 was unable to replicate in normal human ovary samples while the wild-type virus can replicate. This study provides evidence on the lytic capacity of this CRAd and highlights the importance of targeting the stromal tissue in addition to the malignant cell compartment to achieve tumor regression.
Fil: Lopez, Maria Veronica. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquimicas de Buenos Aires; Argentina. Fundación Instituto Leloir; Argentina
Fil: Rivera, Angel A.. University Of Alabama At Birmingahm; Estados Unidos
Fil: Viale, Diego Luis. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquimicas de Buenos Aires; Argentina. Fundación Instituto Leloir; Argentina
Fil: Benedetti, Lorena Gabriela. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquimicas de Buenos Aires; Argentina. Fundación Instituto Leloir; Argentina
Fil: Cuneo, Nicasio. Hospital Municipal de Oncología Marie Curie; Argentina
Fil: Kimball, Kristopher J.. University Of Alabama At Birmingahm; Estados Unidos
Fil: Wang, Minghui. University Of Alabama At Birmingahm. School Of Medicine. Division Of Human Gene Therapy; Estados Unidos
Fil: Douglas, Joanne T.. University Of Alabama At Birmingahm. School Of Medicine. Division Of Human Gene Therapy; Estados Unidos
Fil: Zhu, Zeng B.. University Of Alabama At Birmingahm. School Of Medicine. Division Of Human Gene Therapy; Estados Unidos
Fil: Bravo, Alicia I.. Provincia de Buenos Aires. Ministerio de Salud. Hospital Interzonal de Agudos "eva Peron"; Argentina
Fil: Gidekel, Manuel. Universidad de la Frontera; Chile
Fil: Alvarez, Ronald D.. University Of Alabama At Birmingahm; Estados Unidos
Fil: Curiel, David T.. University Of Alabama At Birmingahm. School Of Medicine. Division Of Human Gene Therapy; Estados Unidos. University of Washington; Estados Unidos
Fil: Podhajcer, Osvaldo Luis. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquimicas de Buenos Aires; Argentina. Fundación Instituto Leloir; Argentina
Materia
CRAd
Ovary
Cancer
Gene therapy
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by-nc-nd/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/15283
Acceder
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oai_identifier_str oai:ri.conicet.gov.ar:11336/15283
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling A tumor-stroma targeted oncolytic adenovirus replicated in human ovary cancer samples and inhibited growth of disseminated solid tumors in miceLopez, Maria VeronicaRivera, Angel A.Viale, Diego LuisBenedetti, Lorena GabrielaCuneo, NicasioKimball, Kristopher J.Wang, MinghuiDouglas, Joanne T.Zhu, Zeng B.Bravo, Alicia I.Gidekel, ManuelAlvarez, Ronald D.Curiel, David T.Podhajcer, Osvaldo LuisCRAdOvaryCancerGene therapyhttps://purl.org/becyt/ford/3.2https://purl.org/becyt/ford/3https://purl.org/becyt/ford/3.2https://purl.org/becyt/ford/3Targeting the tumor stroma in addition to the malignant cell compartment is of paramount importance to achieve complete tumor regression. In this work, we modified a previously designed tumor stroma-targeted conditionally replicative adenovirus (CRAd) based on the SPARC promoter by introducing a mutated E1A unable to bind pRB and pseudotyped with a chimeric Ad5/3 fiber (Ad F512v1), and assessed its replication/lytic capacity in ovary cancer in vitro and in vivo. AdF512v1 was able to replicate in fresh samples obtained from patients: (i) with primary human ovary cancer; (ii) that underwent neoadjuvant treatment; (iii) with metastatic disease. In addition, we show that four intraperitoneal (i.p.) injections of 5 × 10(10) v.p. eliminated 50% of xenografted human ovary tumors disseminated in nude mice. Moreover, AdF512v1 replication in tumor models was enhanced 15-40-fold when the tumor contained a mix of malignant and SPARC-expressing stromal cells (fibroblasts and endothelial cells). Contrary to the wild-type virus, AdF512v1 was unable to replicate in normal human ovary samples while the wild-type virus can replicate. This study provides evidence on the lytic capacity of this CRAd and highlights the importance of targeting the stromal tissue in addition to the malignant cell compartment to achieve tumor regression.Fil: Lopez, Maria Veronica. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquimicas de Buenos Aires; Argentina. Fundación Instituto Leloir; ArgentinaFil: Rivera, Angel A.. University Of Alabama At Birmingahm; Estados UnidosFil: Viale, Diego Luis. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquimicas de Buenos Aires; Argentina. Fundación Instituto Leloir; ArgentinaFil: Benedetti, Lorena Gabriela. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquimicas de Buenos Aires; Argentina. Fundación Instituto Leloir; ArgentinaFil: Cuneo, Nicasio. Hospital Municipal de Oncología Marie Curie; ArgentinaFil: Kimball, Kristopher J.. University Of Alabama At Birmingahm; Estados UnidosFil: Wang, Minghui. University Of Alabama At Birmingahm. School Of Medicine. Division Of Human Gene Therapy; Estados UnidosFil: Douglas, Joanne T.. University Of Alabama At Birmingahm. School Of Medicine. Division Of Human Gene Therapy; Estados UnidosFil: Zhu, Zeng B.. University Of Alabama At Birmingahm. School Of Medicine. Division Of Human Gene Therapy; Estados UnidosFil: Bravo, Alicia I.. Provincia de Buenos Aires. Ministerio de Salud. Hospital Interzonal de Agudos "eva Peron"; ArgentinaFil: Gidekel, Manuel. Universidad de la Frontera; ChileFil: Alvarez, Ronald D.. University Of Alabama At Birmingahm; Estados UnidosFil: Curiel, David T.. University Of Alabama At Birmingahm. School Of Medicine. Division Of Human Gene Therapy; Estados Unidos. University of Washington; Estados UnidosFil: Podhajcer, Osvaldo Luis. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquimicas de Buenos Aires; Argentina. Fundación Instituto Leloir; ArgentinaElsevier2012-12info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/15283Lopez, Maria Veronica; Rivera, Angel A.; Viale, Diego Luis; Benedetti, Lorena Gabriela; Cuneo, Nicasio; et al.; A tumor-stroma targeted oncolytic adenovirus replicated in human ovary cancer samples and inhibited growth of disseminated solid tumors in mice; Elsevier; Molecular Therapy; 20; 12; 12-2012; 2222-22331525-0024enginfo:eu-repo/semantics/altIdentifier/url/http://www.sciencedirect.com/science/article/pii/S1525001616322262info:eu-repo/semantics/altIdentifier/doi/10.1038/mt.2012.147info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-nd/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-03T09:51:27Zoai:ri.conicet.gov.ar:11336/15283instacron:CONICETInstitucionalhttp://ri.conicet.gov.ar/Organismo científico-tecnológicoNo correspondehttp://ri.conicet.gov.ar/oai/requestdasensio@conicet.gov.ar; lcarlino@conicet.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:34982025-09-03 09:51:27.886CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv A tumor-stroma targeted oncolytic adenovirus replicated in human ovary cancer samples and inhibited growth of disseminated solid tumors in mice
title A tumor-stroma targeted oncolytic adenovirus replicated in human ovary cancer samples and inhibited growth of disseminated solid tumors in mice
spellingShingle A tumor-stroma targeted oncolytic adenovirus replicated in human ovary cancer samples and inhibited growth of disseminated solid tumors in mice
Lopez, Maria Veronica
CRAd
Ovary
Cancer
Gene therapy
title_short A tumor-stroma targeted oncolytic adenovirus replicated in human ovary cancer samples and inhibited growth of disseminated solid tumors in mice
title_full A tumor-stroma targeted oncolytic adenovirus replicated in human ovary cancer samples and inhibited growth of disseminated solid tumors in mice
title_fullStr A tumor-stroma targeted oncolytic adenovirus replicated in human ovary cancer samples and inhibited growth of disseminated solid tumors in mice
title_full_unstemmed A tumor-stroma targeted oncolytic adenovirus replicated in human ovary cancer samples and inhibited growth of disseminated solid tumors in mice
title_sort A tumor-stroma targeted oncolytic adenovirus replicated in human ovary cancer samples and inhibited growth of disseminated solid tumors in mice
dc.creator.none.fl_str_mv Lopez, Maria Veronica
Rivera, Angel A.
Viale, Diego Luis
Benedetti, Lorena Gabriela
Cuneo, Nicasio
Kimball, Kristopher J.
Wang, Minghui
Douglas, Joanne T.
Zhu, Zeng B.
Bravo, Alicia I.
Gidekel, Manuel
Alvarez, Ronald D.
Curiel, David T.
Podhajcer, Osvaldo Luis
author Lopez, Maria Veronica
author_facet Lopez, Maria Veronica
Rivera, Angel A.
Viale, Diego Luis
Benedetti, Lorena Gabriela
Cuneo, Nicasio
Kimball, Kristopher J.
Wang, Minghui
Douglas, Joanne T.
Zhu, Zeng B.
Bravo, Alicia I.
Gidekel, Manuel
Alvarez, Ronald D.
Curiel, David T.
Podhajcer, Osvaldo Luis
author_role author
author2 Rivera, Angel A.
Viale, Diego Luis
Benedetti, Lorena Gabriela
Cuneo, Nicasio
Kimball, Kristopher J.
Wang, Minghui
Douglas, Joanne T.
Zhu, Zeng B.
Bravo, Alicia I.
Gidekel, Manuel
Alvarez, Ronald D.
Curiel, David T.
Podhajcer, Osvaldo Luis
author2_role author
author
author
author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv CRAd
Ovary
Cancer
Gene therapy
topic CRAd
Ovary
Cancer
Gene therapy
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.2
https://purl.org/becyt/ford/3
https://purl.org/becyt/ford/3.2
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv Targeting the tumor stroma in addition to the malignant cell compartment is of paramount importance to achieve complete tumor regression. In this work, we modified a previously designed tumor stroma-targeted conditionally replicative adenovirus (CRAd) based on the SPARC promoter by introducing a mutated E1A unable to bind pRB and pseudotyped with a chimeric Ad5/3 fiber (Ad F512v1), and assessed its replication/lytic capacity in ovary cancer in vitro and in vivo. AdF512v1 was able to replicate in fresh samples obtained from patients: (i) with primary human ovary cancer; (ii) that underwent neoadjuvant treatment; (iii) with metastatic disease. In addition, we show that four intraperitoneal (i.p.) injections of 5 × 10(10) v.p. eliminated 50% of xenografted human ovary tumors disseminated in nude mice. Moreover, AdF512v1 replication in tumor models was enhanced 15-40-fold when the tumor contained a mix of malignant and SPARC-expressing stromal cells (fibroblasts and endothelial cells). Contrary to the wild-type virus, AdF512v1 was unable to replicate in normal human ovary samples while the wild-type virus can replicate. This study provides evidence on the lytic capacity of this CRAd and highlights the importance of targeting the stromal tissue in addition to the malignant cell compartment to achieve tumor regression.
Fil: Lopez, Maria Veronica. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquimicas de Buenos Aires; Argentina. Fundación Instituto Leloir; Argentina
Fil: Rivera, Angel A.. University Of Alabama At Birmingahm; Estados Unidos
Fil: Viale, Diego Luis. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquimicas de Buenos Aires; Argentina. Fundación Instituto Leloir; Argentina
Fil: Benedetti, Lorena Gabriela. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquimicas de Buenos Aires; Argentina. Fundación Instituto Leloir; Argentina
Fil: Cuneo, Nicasio. Hospital Municipal de Oncología Marie Curie; Argentina
Fil: Kimball, Kristopher J.. University Of Alabama At Birmingahm; Estados Unidos
Fil: Wang, Minghui. University Of Alabama At Birmingahm. School Of Medicine. Division Of Human Gene Therapy; Estados Unidos
Fil: Douglas, Joanne T.. University Of Alabama At Birmingahm. School Of Medicine. Division Of Human Gene Therapy; Estados Unidos
Fil: Zhu, Zeng B.. University Of Alabama At Birmingahm. School Of Medicine. Division Of Human Gene Therapy; Estados Unidos
Fil: Bravo, Alicia I.. Provincia de Buenos Aires. Ministerio de Salud. Hospital Interzonal de Agudos "eva Peron"; Argentina
Fil: Gidekel, Manuel. Universidad de la Frontera; Chile
Fil: Alvarez, Ronald D.. University Of Alabama At Birmingahm; Estados Unidos
Fil: Curiel, David T.. University Of Alabama At Birmingahm. School Of Medicine. Division Of Human Gene Therapy; Estados Unidos. University of Washington; Estados Unidos
Fil: Podhajcer, Osvaldo Luis. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquimicas de Buenos Aires; Argentina. Fundación Instituto Leloir; Argentina
description Targeting the tumor stroma in addition to the malignant cell compartment is of paramount importance to achieve complete tumor regression. In this work, we modified a previously designed tumor stroma-targeted conditionally replicative adenovirus (CRAd) based on the SPARC promoter by introducing a mutated E1A unable to bind pRB and pseudotyped with a chimeric Ad5/3 fiber (Ad F512v1), and assessed its replication/lytic capacity in ovary cancer in vitro and in vivo. AdF512v1 was able to replicate in fresh samples obtained from patients: (i) with primary human ovary cancer; (ii) that underwent neoadjuvant treatment; (iii) with metastatic disease. In addition, we show that four intraperitoneal (i.p.) injections of 5 × 10(10) v.p. eliminated 50% of xenografted human ovary tumors disseminated in nude mice. Moreover, AdF512v1 replication in tumor models was enhanced 15-40-fold when the tumor contained a mix of malignant and SPARC-expressing stromal cells (fibroblasts and endothelial cells). Contrary to the wild-type virus, AdF512v1 was unable to replicate in normal human ovary samples while the wild-type virus can replicate. This study provides evidence on the lytic capacity of this CRAd and highlights the importance of targeting the stromal tissue in addition to the malignant cell compartment to achieve tumor regression.
publishDate 2012
dc.date.none.fl_str_mv 2012-12
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
http://purl.org/coar/resource_type/c_6501
info:ar-repo/semantics/articulo
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/11336/15283
Lopez, Maria Veronica; Rivera, Angel A.; Viale, Diego Luis; Benedetti, Lorena Gabriela; Cuneo, Nicasio; et al.; A tumor-stroma targeted oncolytic adenovirus replicated in human ovary cancer samples and inhibited growth of disseminated solid tumors in mice; Elsevier; Molecular Therapy; 20; 12; 12-2012; 2222-2233
1525-0024
url http://hdl.handle.net/11336/15283
identifier_str_mv Lopez, Maria Veronica; Rivera, Angel A.; Viale, Diego Luis; Benedetti, Lorena Gabriela; Cuneo, Nicasio; et al.; A tumor-stroma targeted oncolytic adenovirus replicated in human ovary cancer samples and inhibited growth of disseminated solid tumors in mice; Elsevier; Molecular Therapy; 20; 12; 12-2012; 2222-2233
1525-0024
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/url/http://www.sciencedirect.com/science/article/pii/S1525001616322262
info:eu-repo/semantics/altIdentifier/doi/10.1038/mt.2012.147
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by-nc-nd/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by-nc-nd/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
application/pdf
application/pdf
dc.publisher.none.fl_str_mv Elsevier
publisher.none.fl_str_mv Elsevier
dc.source.none.fl_str_mv reponame:CONICET Digital (CONICET)
instname:Consejo Nacional de Investigaciones Científicas y Técnicas
reponame_str CONICET Digital (CONICET)
collection CONICET Digital (CONICET)
instname_str Consejo Nacional de Investigaciones Científicas y Técnicas
repository.name.fl_str_mv CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicas
repository.mail.fl_str_mv dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar
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score 13.13397

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