Defining a murine ovarian cancer model for the evaluation of conditionally-replicative adenovirus (CRAd) virotherapy agents

Autores
González Pastor, Rebeca; Ashshi, Ahmad Mohammad; El Shemi, Adel Galal; Dmitriev, Igor P.; Kashentseva, Elena A.; Lu, Zhi Hong; Goedegebuure, S. Peter; Podhajcer, Osvaldo Luis; Curiel, David T.
Año de publicación
2019
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Background: Virotherapy represents a promising approach for ovarian cancer. In this regard, conditionally replicative adenovirus (CRAd) has been translated to the context of human clinical trials. Advanced design of CRAds has sought to exploit their capacity to induce anti-tumor immunization by configuring immunoregulatory molecule within the CRAd genome. Unfortunately, employed murine xenograft models do not allow full analysis of the immunologic activity linked to CRAd replication. Results: We developed CRAds based on the Ad5/3-Delta24 design encoding cytokines. Whereas the encoded cytokines did not impact adversely CRAd-induced oncolysis in vitro, no gain in anti-tumor activity was noted in immune-incompetent murine models with human ovarian cancer xenografts. On this basis, we explored the potential utility of the murine syngeneic immunocompetent ID8 ovarian cancer model. Of note, the ID8 murine ovarian cancer cell lines exhibited CRAd-mediated cytolysis. The use of this model now enables the rational design of oncolytic agents to achieve anti-tumor immunotherapy. Conclusions: Limits of widely employed murine xenograft models of ovarian cancer limit their utility for design and study of armed CRAd virotherapy agents. The ID8 model exhibited CRAd-induced oncolysis. This feature predicate its potential utility for the study of CRAd-based virotherapy agents.
Fil: González Pastor, Rebeca. Washington University in St. Louis; Estados Unidos
Fil: Ashshi, Ahmad Mohammad. Umm Al Qura University; Arabia Saudita
Fil: El Shemi, Adel Galal. Umm Al Qura University; Arabia Saudita. Assiut University; Egipto
Fil: Dmitriev, Igor P.. Washington University in St. Louis; Estados Unidos
Fil: Kashentseva, Elena A.. Washington University in St. Louis; Estados Unidos
Fil: Lu, Zhi Hong. Washington University in St. Louis; Estados Unidos
Fil: Goedegebuure, S. Peter. Alvin J. Siteman Cancer Center; Estados Unidos. Washington University in St. Louis; Estados Unidos
Fil: Podhajcer, Osvaldo Luis. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; Argentina
Fil: Curiel, David T.. Washington University in St. Louis; Estados Unidos
Materia
ADENOVIRUS
ANTI-TUMOR IMMUNIZATION
CRAD
ID8
OVARIAN CANCER
VIROTHERAPY
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/105170
Acceder
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oai_identifier_str oai:ri.conicet.gov.ar:11336/105170
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Defining a murine ovarian cancer model for the evaluation of conditionally-replicative adenovirus (CRAd) virotherapy agentsGonzález Pastor, RebecaAshshi, Ahmad MohammadEl Shemi, Adel GalalDmitriev, Igor P.Kashentseva, Elena A.Lu, Zhi HongGoedegebuure, S. PeterPodhajcer, Osvaldo LuisCuriel, David T.ADENOVIRUSANTI-TUMOR IMMUNIZATIONCRADID8OVARIAN CANCERVIROTHERAPYhttps://purl.org/becyt/ford/3.1https://purl.org/becyt/ford/3Background: Virotherapy represents a promising approach for ovarian cancer. In this regard, conditionally replicative adenovirus (CRAd) has been translated to the context of human clinical trials. Advanced design of CRAds has sought to exploit their capacity to induce anti-tumor immunization by configuring immunoregulatory molecule within the CRAd genome. Unfortunately, employed murine xenograft models do not allow full analysis of the immunologic activity linked to CRAd replication. Results: We developed CRAds based on the Ad5/3-Delta24 design encoding cytokines. Whereas the encoded cytokines did not impact adversely CRAd-induced oncolysis in vitro, no gain in anti-tumor activity was noted in immune-incompetent murine models with human ovarian cancer xenografts. On this basis, we explored the potential utility of the murine syngeneic immunocompetent ID8 ovarian cancer model. Of note, the ID8 murine ovarian cancer cell lines exhibited CRAd-mediated cytolysis. The use of this model now enables the rational design of oncolytic agents to achieve anti-tumor immunotherapy. Conclusions: Limits of widely employed murine xenograft models of ovarian cancer limit their utility for design and study of armed CRAd virotherapy agents. The ID8 model exhibited CRAd-induced oncolysis. This feature predicate its potential utility for the study of CRAd-based virotherapy agents.Fil: González Pastor, Rebeca. Washington University in St. Louis; Estados UnidosFil: Ashshi, Ahmad Mohammad. Umm Al Qura University; Arabia SauditaFil: El Shemi, Adel Galal. Umm Al Qura University; Arabia Saudita. Assiut University; EgiptoFil: Dmitriev, Igor P.. Washington University in St. Louis; Estados UnidosFil: Kashentseva, Elena A.. Washington University in St. Louis; Estados UnidosFil: Lu, Zhi Hong. Washington University in St. Louis; Estados UnidosFil: Goedegebuure, S. Peter. Alvin J. Siteman Cancer Center; Estados Unidos. Washington University in St. Louis; Estados UnidosFil: Podhajcer, Osvaldo Luis. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; ArgentinaFil: Curiel, David T.. Washington University in St. Louis; Estados UnidosBioMed Central2019-02info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/105170González Pastor, Rebeca; Ashshi, Ahmad Mohammad; El Shemi, Adel Galal; Dmitriev, Igor P.; Kashentseva, Elena A.; et al.; Defining a murine ovarian cancer model for the evaluation of conditionally-replicative adenovirus (CRAd) virotherapy agents; BioMed Central; Journal of Ovarian Research; 12; 18; 2-2019; 1-101757-2215CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/doi/10.1186/s13048-019-0493-5info:eu-repo/semantics/altIdentifier/url/https://ovarianresearch.biomedcentral.com/articles/10.1186/s13048-019-0493-5info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-10T13:03:06Zoai:ri.conicet.gov.ar:11336/105170instacron: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:34982025-09-10 13:03:06.293CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Defining a murine ovarian cancer model for the evaluation of conditionally-replicative adenovirus (CRAd) virotherapy agents
title Defining a murine ovarian cancer model for the evaluation of conditionally-replicative adenovirus (CRAd) virotherapy agents
spellingShingle Defining a murine ovarian cancer model for the evaluation of conditionally-replicative adenovirus (CRAd) virotherapy agents
González Pastor, Rebeca
ADENOVIRUS
ANTI-TUMOR IMMUNIZATION
CRAD
ID8
OVARIAN CANCER
VIROTHERAPY
title_short Defining a murine ovarian cancer model for the evaluation of conditionally-replicative adenovirus (CRAd) virotherapy agents
title_full Defining a murine ovarian cancer model for the evaluation of conditionally-replicative adenovirus (CRAd) virotherapy agents
title_fullStr Defining a murine ovarian cancer model for the evaluation of conditionally-replicative adenovirus (CRAd) virotherapy agents
title_full_unstemmed Defining a murine ovarian cancer model for the evaluation of conditionally-replicative adenovirus (CRAd) virotherapy agents
title_sort Defining a murine ovarian cancer model for the evaluation of conditionally-replicative adenovirus (CRAd) virotherapy agents
dc.creator.none.fl_str_mv González Pastor, Rebeca
Ashshi, Ahmad Mohammad
El Shemi, Adel Galal
Dmitriev, Igor P.
Kashentseva, Elena A.
Lu, Zhi Hong
Goedegebuure, S. Peter
Podhajcer, Osvaldo Luis
Curiel, David T.
author González Pastor, Rebeca
author_facet González Pastor, Rebeca
Ashshi, Ahmad Mohammad
El Shemi, Adel Galal
Dmitriev, Igor P.
Kashentseva, Elena A.
Lu, Zhi Hong
Goedegebuure, S. Peter
Podhajcer, Osvaldo Luis
Curiel, David T.
author_role author
author2 Ashshi, Ahmad Mohammad
El Shemi, Adel Galal
Dmitriev, Igor P.
Kashentseva, Elena A.
Lu, Zhi Hong
Goedegebuure, S. Peter
Podhajcer, Osvaldo Luis
Curiel, David T.
author2_role author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv ADENOVIRUS
ANTI-TUMOR IMMUNIZATION
CRAD
ID8
OVARIAN CANCER
VIROTHERAPY
topic ADENOVIRUS
ANTI-TUMOR IMMUNIZATION
CRAD
ID8
OVARIAN CANCER
VIROTHERAPY
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.1
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv Background: Virotherapy represents a promising approach for ovarian cancer. In this regard, conditionally replicative adenovirus (CRAd) has been translated to the context of human clinical trials. Advanced design of CRAds has sought to exploit their capacity to induce anti-tumor immunization by configuring immunoregulatory molecule within the CRAd genome. Unfortunately, employed murine xenograft models do not allow full analysis of the immunologic activity linked to CRAd replication. Results: We developed CRAds based on the Ad5/3-Delta24 design encoding cytokines. Whereas the encoded cytokines did not impact adversely CRAd-induced oncolysis in vitro, no gain in anti-tumor activity was noted in immune-incompetent murine models with human ovarian cancer xenografts. On this basis, we explored the potential utility of the murine syngeneic immunocompetent ID8 ovarian cancer model. Of note, the ID8 murine ovarian cancer cell lines exhibited CRAd-mediated cytolysis. The use of this model now enables the rational design of oncolytic agents to achieve anti-tumor immunotherapy. Conclusions: Limits of widely employed murine xenograft models of ovarian cancer limit their utility for design and study of armed CRAd virotherapy agents. The ID8 model exhibited CRAd-induced oncolysis. This feature predicate its potential utility for the study of CRAd-based virotherapy agents.
Fil: González Pastor, Rebeca. Washington University in St. Louis; Estados Unidos
Fil: Ashshi, Ahmad Mohammad. Umm Al Qura University; Arabia Saudita
Fil: El Shemi, Adel Galal. Umm Al Qura University; Arabia Saudita. Assiut University; Egipto
Fil: Dmitriev, Igor P.. Washington University in St. Louis; Estados Unidos
Fil: Kashentseva, Elena A.. Washington University in St. Louis; Estados Unidos
Fil: Lu, Zhi Hong. Washington University in St. Louis; Estados Unidos
Fil: Goedegebuure, S. Peter. Alvin J. Siteman Cancer Center; Estados Unidos. Washington University in St. Louis; Estados Unidos
Fil: Podhajcer, Osvaldo Luis. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; Argentina
Fil: Curiel, David T.. Washington University in St. Louis; Estados Unidos
description Background: Virotherapy represents a promising approach for ovarian cancer. In this regard, conditionally replicative adenovirus (CRAd) has been translated to the context of human clinical trials. Advanced design of CRAds has sought to exploit their capacity to induce anti-tumor immunization by configuring immunoregulatory molecule within the CRAd genome. Unfortunately, employed murine xenograft models do not allow full analysis of the immunologic activity linked to CRAd replication. Results: We developed CRAds based on the Ad5/3-Delta24 design encoding cytokines. Whereas the encoded cytokines did not impact adversely CRAd-induced oncolysis in vitro, no gain in anti-tumor activity was noted in immune-incompetent murine models with human ovarian cancer xenografts. On this basis, we explored the potential utility of the murine syngeneic immunocompetent ID8 ovarian cancer model. Of note, the ID8 murine ovarian cancer cell lines exhibited CRAd-mediated cytolysis. The use of this model now enables the rational design of oncolytic agents to achieve anti-tumor immunotherapy. Conclusions: Limits of widely employed murine xenograft models of ovarian cancer limit their utility for design and study of armed CRAd virotherapy agents. The ID8 model exhibited CRAd-induced oncolysis. This feature predicate its potential utility for the study of CRAd-based virotherapy agents.
publishDate 2019
dc.date.none.fl_str_mv 2019-02
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/11336/105170
González Pastor, Rebeca; Ashshi, Ahmad Mohammad; El Shemi, Adel Galal; Dmitriev, Igor P.; Kashentseva, Elena A.; et al.; Defining a murine ovarian cancer model for the evaluation of conditionally-replicative adenovirus (CRAd) virotherapy agents; BioMed Central; Journal of Ovarian Research; 12; 18; 2-2019; 1-10
1757-2215
CONICET Digital
CONICET
url http://hdl.handle.net/11336/105170
identifier_str_mv González Pastor, Rebeca; Ashshi, Ahmad Mohammad; El Shemi, Adel Galal; Dmitriev, Igor P.; Kashentseva, Elena A.; et al.; Defining a murine ovarian cancer model for the evaluation of conditionally-replicative adenovirus (CRAd) virotherapy agents; BioMed Central; Journal of Ovarian Research; 12; 18; 2-2019; 1-10
1757-2215
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/doi/10.1186/s13048-019-0493-5
info:eu-repo/semantics/altIdentifier/url/https://ovarianresearch.biomedcentral.com/articles/10.1186/s13048-019-0493-5
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
dc.publisher.none.fl_str_mv BioMed Central
publisher.none.fl_str_mv BioMed Central
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 12.993085

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