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Enhanced Delivery of Oncolytic Adenovirus by Neural Stem Cells for Treatment of Metastatic Ovarian Cancer

Oncolytic virotherapy is a promising approach for treating recurrent and/or drug-resistant ovarian cancer. However, its successful application in the clinic has been hampered by rapid immune-mediated clearance or neutralization of the virus, which reduces viral access to tumor foci. To overcome this...

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Autores principales: Mooney, Rachael, Majid, Asma Abdul, Batalla-Covello, Jennifer, Machado, Diana, Liu, Xueli, Gonzaga, Joanna, Tirughana, Revathiswari, Hammad, Mohamed, Lesniak, Maciej S., Curiel, David T., Aboody, Karen S.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Society of Gene & Cell Therapy 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6350263/
https://www.ncbi.nlm.nih.gov/pubmed/30719498
http://dx.doi.org/10.1016/j.omto.2018.12.003
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author Mooney, Rachael
Majid, Asma Abdul
Batalla-Covello, Jennifer
Machado, Diana
Liu, Xueli
Gonzaga, Joanna
Tirughana, Revathiswari
Hammad, Mohamed
Lesniak, Maciej S.
Curiel, David T.
Aboody, Karen S.
author_facet Mooney, Rachael
Majid, Asma Abdul
Batalla-Covello, Jennifer
Machado, Diana
Liu, Xueli
Gonzaga, Joanna
Tirughana, Revathiswari
Hammad, Mohamed
Lesniak, Maciej S.
Curiel, David T.
Aboody, Karen S.
author_sort Mooney, Rachael
collection PubMed
description Oncolytic virotherapy is a promising approach for treating recurrent and/or drug-resistant ovarian cancer. However, its successful application in the clinic has been hampered by rapid immune-mediated clearance or neutralization of the virus, which reduces viral access to tumor foci. To overcome this barrier, patient-derived mesenchymal stem cells have been used to deliver virus to tumors, but variability associated with autologous cell isolations prevents this approach from being broadly clinically applicable. Here, we demonstrate the ability of an allogeneic, clonal neural stem cell (NSC) line (HB1.F3.CD21) to protect oncolytic viral cargo from neutralizing antibodies within patient ascites fluid and to deliver it to tumors within preclinical peritoneal ovarian metastases models. The viral payload used is a conditionally replication-competent adenovirus driven by the survivin promoter (CRAd-S-pk7). Because the protein survivin is highly expressed in ovarian cancer, but not in normal differentiated cells, viral replication should occur selectively in ovarian tumor cells. We found this viral agent was effective against cisplatin-resistant ovarian tumors and could be used as an adjunct treatment with cisplatin to decrease tumor burden without increasing toxicity. Collectively, our data suggest NSC-delivered CRAd-S-pk7 virotherapy holds promise for improving clinical outcome, reducing toxicities, and improving quality of life for patients with advanced ovarian cancer.
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spelling pubmed-63502632019-02-04 Enhanced Delivery of Oncolytic Adenovirus by Neural Stem Cells for Treatment of Metastatic Ovarian Cancer Mooney, Rachael Majid, Asma Abdul Batalla-Covello, Jennifer Machado, Diana Liu, Xueli Gonzaga, Joanna Tirughana, Revathiswari Hammad, Mohamed Lesniak, Maciej S. Curiel, David T. Aboody, Karen S. Mol Ther Oncolytics Article Oncolytic virotherapy is a promising approach for treating recurrent and/or drug-resistant ovarian cancer. However, its successful application in the clinic has been hampered by rapid immune-mediated clearance or neutralization of the virus, which reduces viral access to tumor foci. To overcome this barrier, patient-derived mesenchymal stem cells have been used to deliver virus to tumors, but variability associated with autologous cell isolations prevents this approach from being broadly clinically applicable. Here, we demonstrate the ability of an allogeneic, clonal neural stem cell (NSC) line (HB1.F3.CD21) to protect oncolytic viral cargo from neutralizing antibodies within patient ascites fluid and to deliver it to tumors within preclinical peritoneal ovarian metastases models. The viral payload used is a conditionally replication-competent adenovirus driven by the survivin promoter (CRAd-S-pk7). Because the protein survivin is highly expressed in ovarian cancer, but not in normal differentiated cells, viral replication should occur selectively in ovarian tumor cells. We found this viral agent was effective against cisplatin-resistant ovarian tumors and could be used as an adjunct treatment with cisplatin to decrease tumor burden without increasing toxicity. Collectively, our data suggest NSC-delivered CRAd-S-pk7 virotherapy holds promise for improving clinical outcome, reducing toxicities, and improving quality of life for patients with advanced ovarian cancer. American Society of Gene & Cell Therapy 2018-12-13 /pmc/articles/PMC6350263/ /pubmed/30719498 http://dx.doi.org/10.1016/j.omto.2018.12.003 Text en © 2018 The Author(s) http://creativecommons.org/licenses/by-nc-nd/4.0/ This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
spellingShingle Article
Mooney, Rachael
Majid, Asma Abdul
Batalla-Covello, Jennifer
Machado, Diana
Liu, Xueli
Gonzaga, Joanna
Tirughana, Revathiswari
Hammad, Mohamed
Lesniak, Maciej S.
Curiel, David T.
Aboody, Karen S.
Enhanced Delivery of Oncolytic Adenovirus by Neural Stem Cells for Treatment of Metastatic Ovarian Cancer
title Enhanced Delivery of Oncolytic Adenovirus by Neural Stem Cells for Treatment of Metastatic Ovarian Cancer
title_full Enhanced Delivery of Oncolytic Adenovirus by Neural Stem Cells for Treatment of Metastatic Ovarian Cancer
title_fullStr Enhanced Delivery of Oncolytic Adenovirus by Neural Stem Cells for Treatment of Metastatic Ovarian Cancer
title_full_unstemmed Enhanced Delivery of Oncolytic Adenovirus by Neural Stem Cells for Treatment of Metastatic Ovarian Cancer
title_short Enhanced Delivery of Oncolytic Adenovirus by Neural Stem Cells for Treatment of Metastatic Ovarian Cancer
title_sort enhanced delivery of oncolytic adenovirus by neural stem cells for treatment of metastatic ovarian cancer
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6350263/
https://www.ncbi.nlm.nih.gov/pubmed/30719498
http://dx.doi.org/10.1016/j.omto.2018.12.003
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