Enhanced antitumor efficacy of an oncolytic adenovirus armed with an EGFR-targeted BiTE using menstrual blood-derived mesenchymal stem cells as carriers

Poor tumor targeting of oncolytic adenoviruses (OAdv) after systemic administration is considered a major limitation for virotherapy of disseminated cancers. The benefit of using mesenchymal stem cells as cell carriers for OAdv tumor targeting is currently evaluated not only in preclinical models bu...

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Detalles Bibliográficos
Autores: Barlabé, Paula, Sostoa, Jana de, Fajardo Calderón, Carlos Alberto, Alemany Bonastre, Ramon, Moreno Olié, Rafael
Tipo de recurso: artículo
Estado:Versión aceptada para publicación
Fecha de publicación:2019
País:España
Institución:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
Repositorio:Recercat. Dipósit de la Recerca de Catalunya
OAI Identifier:oai:recercat.cat:2445/139717
Acceso en línea:https://hdl.handle.net/2445/139717
Access Level:acceso abierto
Palabra clave:Adenovirus
Adenoviruses
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spelling Enhanced antitumor efficacy of an oncolytic adenovirus armed with an EGFR-targeted BiTE using menstrual blood-derived mesenchymal stem cells as carriersBarlabé, PaulaSostoa, Jana deFajardo Calderón, Carlos AlbertoAlemany Bonastre, RamonMoreno Olié, RafaelAdenovirusAdenovirusesPoor tumor targeting of oncolytic adenoviruses (OAdv) after systemic administration is considered a major limitation for virotherapy of disseminated cancers. The benefit of using mesenchymal stem cells as cell carriers for OAdv tumor targeting is currently evaluated not only in preclinical models but also in clinical trials. In this context, we have previously demonstrated the enhanced antitumor efficacy of OAdv-loaded menstrual blood-derived mesenchymal stem cells (MenSCs). However, although significant, the antitumor efficacy obtained was modest, and we hypothesized that a greater antitumor efficacy could be obtained arming the OAdv with a therapeutic transgene. Here we show that combining MenSCs with ICOVIR15-cBiTE, an OAdv expressing an epidermal growth factor receptor (EGFR)-targeting bispecific T-cell engager (cBiTE), enhances the antitumor efficacy compared to MenSCs loaded with the unarmed virus ICOVIR15. We found that MenSCs properly produce cBiTE after viral infection leading to a greater antitumor potency both in vitro and in vivo. These findings indicate the mutual benefit of combining MenSCs and armed OAdv and support the combination of ICOVIR15-cBiTE and MenSCs as a cancer treatment.We thank CERCA Program/Generalitat de Catalunya for their institutional support. The authors also thank Dolores Ramos and Silvia Torres for their lab technical support and Vanessa Cervera for samples processing. This work was supported by the Asociación Española Contra el Cáncer, BIO2017-897554-C2-1-Rgrant to R. Alemany from the Ministerio de Economía y Competitividad of Spain, Adenonet BIO2015-68990-REDT to R. Alemany from the Ministerio de Economía y Competitividad of Spain, RedADVANCE(CAT) project COMRDI15-1-0013 to R. Alemany from Ris3CAT and 2017SGR449 research grant to RA from the ‘Generalitat de Catalunya’. Cofunded by the European Regional Development Fund, a way to Build Europe to RA.Springer Nature201920192019info:eu-repo/semantics/articleinfo:eu-repo/semantics/acceptedVersion16 p.application/pdfhttps://hdl.handle.net/2445/139717Articles publicats en revistes (Institut d'lnvestigació Biomèdica de Bellvitge (IDIBELL))reponame:Recercat. Dipósit de la Recerca de Catalunyainstname:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)InglésVersió postprint de l'article publicat a: https://doi.org/10.1038/s41417-019-0110-1Cancer Gene Therapy, 2019(c) Springer Nature, 2019info:eu-repo/semantics/openAccessoai:recercat.cat:2445/1397172026-05-29T05:05:01Z
dc.title.none.fl_str_mv Enhanced antitumor efficacy of an oncolytic adenovirus armed with an EGFR-targeted BiTE using menstrual blood-derived mesenchymal stem cells as carriers
title Enhanced antitumor efficacy of an oncolytic adenovirus armed with an EGFR-targeted BiTE using menstrual blood-derived mesenchymal stem cells as carriers
spellingShingle Enhanced antitumor efficacy of an oncolytic adenovirus armed with an EGFR-targeted BiTE using menstrual blood-derived mesenchymal stem cells as carriers
Barlabé, Paula
Adenovirus
Adenoviruses
title_short Enhanced antitumor efficacy of an oncolytic adenovirus armed with an EGFR-targeted BiTE using menstrual blood-derived mesenchymal stem cells as carriers
title_full Enhanced antitumor efficacy of an oncolytic adenovirus armed with an EGFR-targeted BiTE using menstrual blood-derived mesenchymal stem cells as carriers
title_fullStr Enhanced antitumor efficacy of an oncolytic adenovirus armed with an EGFR-targeted BiTE using menstrual blood-derived mesenchymal stem cells as carriers
title_full_unstemmed Enhanced antitumor efficacy of an oncolytic adenovirus armed with an EGFR-targeted BiTE using menstrual blood-derived mesenchymal stem cells as carriers
title_sort Enhanced antitumor efficacy of an oncolytic adenovirus armed with an EGFR-targeted BiTE using menstrual blood-derived mesenchymal stem cells as carriers
dc.creator.none.fl_str_mv Barlabé, Paula
Sostoa, Jana de
Fajardo Calderón, Carlos Alberto
Alemany Bonastre, Ramon
Moreno Olié, Rafael
author Barlabé, Paula
author_facet Barlabé, Paula
Sostoa, Jana de
Fajardo Calderón, Carlos Alberto
Alemany Bonastre, Ramon
Moreno Olié, Rafael
author_role author
author2 Sostoa, Jana de
Fajardo Calderón, Carlos Alberto
Alemany Bonastre, Ramon
Moreno Olié, Rafael
author2_role author
author
author
author
dc.subject.none.fl_str_mv Adenovirus
Adenoviruses
topic Adenovirus
Adenoviruses
description Poor tumor targeting of oncolytic adenoviruses (OAdv) after systemic administration is considered a major limitation for virotherapy of disseminated cancers. The benefit of using mesenchymal stem cells as cell carriers for OAdv tumor targeting is currently evaluated not only in preclinical models but also in clinical trials. In this context, we have previously demonstrated the enhanced antitumor efficacy of OAdv-loaded menstrual blood-derived mesenchymal stem cells (MenSCs). However, although significant, the antitumor efficacy obtained was modest, and we hypothesized that a greater antitumor efficacy could be obtained arming the OAdv with a therapeutic transgene. Here we show that combining MenSCs with ICOVIR15-cBiTE, an OAdv expressing an epidermal growth factor receptor (EGFR)-targeting bispecific T-cell engager (cBiTE), enhances the antitumor efficacy compared to MenSCs loaded with the unarmed virus ICOVIR15. We found that MenSCs properly produce cBiTE after viral infection leading to a greater antitumor potency both in vitro and in vivo. These findings indicate the mutual benefit of combining MenSCs and armed OAdv and support the combination of ICOVIR15-cBiTE and MenSCs as a cancer treatment.
publishDate 2019
dc.date.none.fl_str_mv 2019
2019
2019
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/acceptedVersion
format article
status_str acceptedVersion
dc.identifier.none.fl_str_mv https://hdl.handle.net/2445/139717
url https://hdl.handle.net/2445/139717
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv Versió postprint de l'article publicat a: https://doi.org/10.1038/s41417-019-0110-1
Cancer Gene Therapy, 2019
dc.rights.none.fl_str_mv (c) Springer Nature, 2019
info:eu-repo/semantics/openAccess
rights_invalid_str_mv (c) Springer Nature, 2019
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv 16 p.
application/pdf
dc.publisher.none.fl_str_mv Springer Nature
publisher.none.fl_str_mv Springer Nature
dc.source.none.fl_str_mv Articles publicats en revistes (Institut d'lnvestigació Biomèdica de Bellvitge (IDIBELL))
reponame:Recercat. Dipósit de la Recerca de Catalunya
instname:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
instname_str Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
reponame_str Recercat. Dipósit de la Recerca de Catalunya
collection Recercat. Dipósit de la Recerca de Catalunya
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15,81155

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