Oncolytic Adenovirus-Loaded Menstrual Blood Stem Cells Overcome the Blockade of Viral Activity Exerted by Ovarian Cancer Ascites

Autores
Alfano, Ana Laura; Nicola Candia, Alejandro Javier; Cuneo, Nicasio; Guttlein, Leandro N.; Soderini, Alejandro; Rotondaro, Cecilia; Sganga, Leonardo; Podhajcer, Osvaldo Luis; Lopez, Maria Veronica
Año de publicación
2017
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Patients with ovarian cancer present peritoneal ascites at recurrence as a marker of disseminated disease and dismal prognosis. Oncolytic immunotherapy is an emerging approach for the treatment of disseminated cancer. In the present work, we constructed a novel oncolytic adenovirus, AR2011, to target malignant ovarian tumors. AR2011 exhibited a clear lytic effect in vitro in human ovarian cancer cell lines and malignant cells obtained from ascitic fluids (AFs) of patients with ovarian cancer. AR2011 activity was neutralized by antibodies present in 31 samples of patient-derived AFs. However, this blockade was overridden by preloading menstrual blood stem cells (MenSCs) with AR2011 (MenSC-AR), since AFs exerted no in vitro inhibitory effect on viral lytic activity under these conditions. Moreover, soluble factors present in AFs act as MenSC chemoattractants. MenSC-AR treatment of nude mice carrying established peritoneal carcinomatosis following administration of human ovarian cancer cells was able to inhibit tumor growth at levels similar to those observed with AR2011 alone. This study demonstrates that MenSCs can be used to override the blockade that AFs exert on viral oncolytic effects.
Fil: Alfano, Ana Laura. 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: Nicola Candia, Alejandro Javier. 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: Cuneo, Nicasio. Hospital Municipal de Oncología Marie Curie; Argentina
Fil: Guttlein, Leandro N.. 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: Soderini, Alejandro. Hospital Municipal de Oncología Marie Curie; Argentina
Fil: Rotondaro, Cecilia. 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: Sganga, Leonardo. 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: 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: Lopez, Maria Veronica. 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
Materia
CRAD
MSC
OVARIAN CANCER
PERITONEAL CARCINOSIS
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/63279

id CONICETDig_2dd16b845f3feac5083d31569f1018a1
oai_identifier_str oai:ri.conicet.gov.ar:11336/63279
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Oncolytic Adenovirus-Loaded Menstrual Blood Stem Cells Overcome the Blockade of Viral Activity Exerted by Ovarian Cancer AscitesAlfano, Ana LauraNicola Candia, Alejandro JavierCuneo, NicasioGuttlein, Leandro N.Soderini, AlejandroRotondaro, CeciliaSganga, LeonardoPodhajcer, Osvaldo LuisLopez, Maria VeronicaCRADMSCOVARIAN CANCERPERITONEAL CARCINOSIShttps://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1Patients with ovarian cancer present peritoneal ascites at recurrence as a marker of disseminated disease and dismal prognosis. Oncolytic immunotherapy is an emerging approach for the treatment of disseminated cancer. In the present work, we constructed a novel oncolytic adenovirus, AR2011, to target malignant ovarian tumors. AR2011 exhibited a clear lytic effect in vitro in human ovarian cancer cell lines and malignant cells obtained from ascitic fluids (AFs) of patients with ovarian cancer. AR2011 activity was neutralized by antibodies present in 31 samples of patient-derived AFs. However, this blockade was overridden by preloading menstrual blood stem cells (MenSCs) with AR2011 (MenSC-AR), since AFs exerted no in vitro inhibitory effect on viral lytic activity under these conditions. Moreover, soluble factors present in AFs act as MenSC chemoattractants. MenSC-AR treatment of nude mice carrying established peritoneal carcinomatosis following administration of human ovarian cancer cells was able to inhibit tumor growth at levels similar to those observed with AR2011 alone. This study demonstrates that MenSCs can be used to override the blockade that AFs exert on viral oncolytic effects.Fil: Alfano, Ana Laura. 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: Nicola Candia, Alejandro Javier. 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: Cuneo, Nicasio. Hospital Municipal de Oncología Marie Curie; ArgentinaFil: Guttlein, Leandro N.. 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: Soderini, Alejandro. Hospital Municipal de Oncología Marie Curie; ArgentinaFil: Rotondaro, Cecilia. 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: Sganga, Leonardo. 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: 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: Lopez, Maria Veronica. 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; ArgentinaAmerican Society of Gene and Cell Therapy2017-09info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/63279Alfano, Ana Laura; Nicola Candia, Alejandro Javier; Cuneo, Nicasio; Guttlein, Leandro N.; Soderini, Alejandro; et al.; Oncolytic Adenovirus-Loaded Menstrual Blood Stem Cells Overcome the Blockade of Viral Activity Exerted by Ovarian Cancer Ascites; American Society of Gene and Cell Therapy; Molecular Therapy - Oncolytics; 6; 9-2017; 31-442372-77052372-7705CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://www.sciencedirect.com/science/article/pii/S237277051730027Xinfo:eu-repo/semantics/altIdentifier/doi/10.1016/j.omto.2017.06.002info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-29T10:00:41Zoai:ri.conicet.gov.ar:11336/63279instacron: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:34982025-09-29 10:00:41.462CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Oncolytic Adenovirus-Loaded Menstrual Blood Stem Cells Overcome the Blockade of Viral Activity Exerted by Ovarian Cancer Ascites
title Oncolytic Adenovirus-Loaded Menstrual Blood Stem Cells Overcome the Blockade of Viral Activity Exerted by Ovarian Cancer Ascites
spellingShingle Oncolytic Adenovirus-Loaded Menstrual Blood Stem Cells Overcome the Blockade of Viral Activity Exerted by Ovarian Cancer Ascites
Alfano, Ana Laura
CRAD
MSC
OVARIAN CANCER
PERITONEAL CARCINOSIS
title_short Oncolytic Adenovirus-Loaded Menstrual Blood Stem Cells Overcome the Blockade of Viral Activity Exerted by Ovarian Cancer Ascites
title_full Oncolytic Adenovirus-Loaded Menstrual Blood Stem Cells Overcome the Blockade of Viral Activity Exerted by Ovarian Cancer Ascites
title_fullStr Oncolytic Adenovirus-Loaded Menstrual Blood Stem Cells Overcome the Blockade of Viral Activity Exerted by Ovarian Cancer Ascites
title_full_unstemmed Oncolytic Adenovirus-Loaded Menstrual Blood Stem Cells Overcome the Blockade of Viral Activity Exerted by Ovarian Cancer Ascites
title_sort Oncolytic Adenovirus-Loaded Menstrual Blood Stem Cells Overcome the Blockade of Viral Activity Exerted by Ovarian Cancer Ascites
dc.creator.none.fl_str_mv Alfano, Ana Laura
Nicola Candia, Alejandro Javier
Cuneo, Nicasio
Guttlein, Leandro N.
Soderini, Alejandro
Rotondaro, Cecilia
Sganga, Leonardo
Podhajcer, Osvaldo Luis
Lopez, Maria Veronica
author Alfano, Ana Laura
author_facet Alfano, Ana Laura
Nicola Candia, Alejandro Javier
Cuneo, Nicasio
Guttlein, Leandro N.
Soderini, Alejandro
Rotondaro, Cecilia
Sganga, Leonardo
Podhajcer, Osvaldo Luis
Lopez, Maria Veronica
author_role author
author2 Nicola Candia, Alejandro Javier
Cuneo, Nicasio
Guttlein, Leandro N.
Soderini, Alejandro
Rotondaro, Cecilia
Sganga, Leonardo
Podhajcer, Osvaldo Luis
Lopez, Maria Veronica
author2_role author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv CRAD
MSC
OVARIAN CANCER
PERITONEAL CARCINOSIS
topic CRAD
MSC
OVARIAN CANCER
PERITONEAL CARCINOSIS
purl_subject.fl_str_mv https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
dc.description.none.fl_txt_mv Patients with ovarian cancer present peritoneal ascites at recurrence as a marker of disseminated disease and dismal prognosis. Oncolytic immunotherapy is an emerging approach for the treatment of disseminated cancer. In the present work, we constructed a novel oncolytic adenovirus, AR2011, to target malignant ovarian tumors. AR2011 exhibited a clear lytic effect in vitro in human ovarian cancer cell lines and malignant cells obtained from ascitic fluids (AFs) of patients with ovarian cancer. AR2011 activity was neutralized by antibodies present in 31 samples of patient-derived AFs. However, this blockade was overridden by preloading menstrual blood stem cells (MenSCs) with AR2011 (MenSC-AR), since AFs exerted no in vitro inhibitory effect on viral lytic activity under these conditions. Moreover, soluble factors present in AFs act as MenSC chemoattractants. MenSC-AR treatment of nude mice carrying established peritoneal carcinomatosis following administration of human ovarian cancer cells was able to inhibit tumor growth at levels similar to those observed with AR2011 alone. This study demonstrates that MenSCs can be used to override the blockade that AFs exert on viral oncolytic effects.
Fil: Alfano, Ana Laura. 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: Nicola Candia, Alejandro Javier. 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: Cuneo, Nicasio. Hospital Municipal de Oncología Marie Curie; Argentina
Fil: Guttlein, Leandro N.. 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: Soderini, Alejandro. Hospital Municipal de Oncología Marie Curie; Argentina
Fil: Rotondaro, Cecilia. 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: Sganga, Leonardo. 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: 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: Lopez, Maria Veronica. 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
description Patients with ovarian cancer present peritoneal ascites at recurrence as a marker of disseminated disease and dismal prognosis. Oncolytic immunotherapy is an emerging approach for the treatment of disseminated cancer. In the present work, we constructed a novel oncolytic adenovirus, AR2011, to target malignant ovarian tumors. AR2011 exhibited a clear lytic effect in vitro in human ovarian cancer cell lines and malignant cells obtained from ascitic fluids (AFs) of patients with ovarian cancer. AR2011 activity was neutralized by antibodies present in 31 samples of patient-derived AFs. However, this blockade was overridden by preloading menstrual blood stem cells (MenSCs) with AR2011 (MenSC-AR), since AFs exerted no in vitro inhibitory effect on viral lytic activity under these conditions. Moreover, soluble factors present in AFs act as MenSC chemoattractants. MenSC-AR treatment of nude mice carrying established peritoneal carcinomatosis following administration of human ovarian cancer cells was able to inhibit tumor growth at levels similar to those observed with AR2011 alone. This study demonstrates that MenSCs can be used to override the blockade that AFs exert on viral oncolytic effects.
publishDate 2017
dc.date.none.fl_str_mv 2017-09
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/11336/63279
Alfano, Ana Laura; Nicola Candia, Alejandro Javier; Cuneo, Nicasio; Guttlein, Leandro N.; Soderini, Alejandro; et al.; Oncolytic Adenovirus-Loaded Menstrual Blood Stem Cells Overcome the Blockade of Viral Activity Exerted by Ovarian Cancer Ascites; American Society of Gene and Cell Therapy; Molecular Therapy - Oncolytics; 6; 9-2017; 31-44
2372-7705
2372-7705
CONICET Digital
CONICET
url http://hdl.handle.net/11336/63279
identifier_str_mv Alfano, Ana Laura; Nicola Candia, Alejandro Javier; Cuneo, Nicasio; Guttlein, Leandro N.; Soderini, Alejandro; et al.; Oncolytic Adenovirus-Loaded Menstrual Blood Stem Cells Overcome the Blockade of Viral Activity Exerted by Ovarian Cancer Ascites; American Society of Gene and Cell Therapy; Molecular Therapy - Oncolytics; 6; 9-2017; 31-44
2372-7705
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/url/https://www.sciencedirect.com/science/article/pii/S237277051730027X
info:eu-repo/semantics/altIdentifier/doi/10.1016/j.omto.2017.06.002
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
application/pdf
application/pdf
application/pdf
dc.publisher.none.fl_str_mv American Society of Gene and Cell Therapy
publisher.none.fl_str_mv American Society of Gene and Cell Therapy
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
_version_ 1844613791078154240
score 13.070432