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Novel Chimeric Poxvirus CF17 Improves Survival in a Murine Model of Intraperitoneal Ovarian Cancer Metastasis

Despite improvements in surgical techniques and chemotherapy, ovarian cancer remains the most lethal gynecologic cancer. Thus, there is an urgent need for more effective therapeutics, particularly for chemo-resistant peritoneal ovarian cancer metastases. Oncolytic virotherapy represents an innovativ...

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Autores principales: Hammad, Mohamed, Cornejo, Yvonne, Flores, Linda, Hyde, Caitlyn, Ngai, Hoi Wa, Li, Min, Dellinger, Thanh H., Lu, Jianming, Chen, Nanhai G., Mooney, Rachael, Aboody, Karen S., Fong, Yuman
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Society of Gene & Cell Therapy 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7672245/
https://www.ncbi.nlm.nih.gov/pubmed/33251335
http://dx.doi.org/10.1016/j.omto.2020.10.002
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author Hammad, Mohamed
Cornejo, Yvonne
Flores, Linda
Hyde, Caitlyn
Ngai, Hoi Wa
Li, Min
Dellinger, Thanh H.
Lu, Jianming
Chen, Nanhai G.
Mooney, Rachael
Aboody, Karen S.
Fong, Yuman
author_facet Hammad, Mohamed
Cornejo, Yvonne
Flores, Linda
Hyde, Caitlyn
Ngai, Hoi Wa
Li, Min
Dellinger, Thanh H.
Lu, Jianming
Chen, Nanhai G.
Mooney, Rachael
Aboody, Karen S.
Fong, Yuman
author_sort Hammad, Mohamed
collection PubMed
description Despite improvements in surgical techniques and chemotherapy, ovarian cancer remains the most lethal gynecologic cancer. Thus, there is an urgent need for more effective therapeutics, particularly for chemo-resistant peritoneal ovarian cancer metastases. Oncolytic virotherapy represents an innovative treatment paradigm; however, for oncolytic viruses tested from the last generation of genetically engineered viruses, the therapeutic benefits have been modest. To overcome these limitations, we generated a chimeric poxvirus, CF17, through the chimerization of nine species of orthopoxviruses. Compared with its parental viruses, CF17 has demonstrated superior oncolytic characteristics. Here, we report the oncolytic potential of CF17 in ovarian cancer. Replication of CF17 and its resulting cytotoxicity were observed at multiplicities of infection (MOIs) as low as 0.001 in human and mouse cancer cell lines in vitro. Furthermore, CF17 exerted potent antitumor effects in a syngeneic mouse model of ovarian cancer at doses as low as 6 × 10(6) plaque-forming units. Together, these data merit further investigation of the potential use of this novel chimeric poxvirus as an effective treatment for aggressive intraperitoneal ovarian cancer.
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spelling pubmed-76722452020-11-27 Novel Chimeric Poxvirus CF17 Improves Survival in a Murine Model of Intraperitoneal Ovarian Cancer Metastasis Hammad, Mohamed Cornejo, Yvonne Flores, Linda Hyde, Caitlyn Ngai, Hoi Wa Li, Min Dellinger, Thanh H. Lu, Jianming Chen, Nanhai G. Mooney, Rachael Aboody, Karen S. Fong, Yuman Mol Ther Oncolytics Original Article Despite improvements in surgical techniques and chemotherapy, ovarian cancer remains the most lethal gynecologic cancer. Thus, there is an urgent need for more effective therapeutics, particularly for chemo-resistant peritoneal ovarian cancer metastases. Oncolytic virotherapy represents an innovative treatment paradigm; however, for oncolytic viruses tested from the last generation of genetically engineered viruses, the therapeutic benefits have been modest. To overcome these limitations, we generated a chimeric poxvirus, CF17, through the chimerization of nine species of orthopoxviruses. Compared with its parental viruses, CF17 has demonstrated superior oncolytic characteristics. Here, we report the oncolytic potential of CF17 in ovarian cancer. Replication of CF17 and its resulting cytotoxicity were observed at multiplicities of infection (MOIs) as low as 0.001 in human and mouse cancer cell lines in vitro. Furthermore, CF17 exerted potent antitumor effects in a syngeneic mouse model of ovarian cancer at doses as low as 6 × 10(6) plaque-forming units. Together, these data merit further investigation of the potential use of this novel chimeric poxvirus as an effective treatment for aggressive intraperitoneal ovarian cancer. American Society of Gene & Cell Therapy 2020-10-10 /pmc/articles/PMC7672245/ /pubmed/33251335 http://dx.doi.org/10.1016/j.omto.2020.10.002 Text en © 2020 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 Original Article
Hammad, Mohamed
Cornejo, Yvonne
Flores, Linda
Hyde, Caitlyn
Ngai, Hoi Wa
Li, Min
Dellinger, Thanh H.
Lu, Jianming
Chen, Nanhai G.
Mooney, Rachael
Aboody, Karen S.
Fong, Yuman
Novel Chimeric Poxvirus CF17 Improves Survival in a Murine Model of Intraperitoneal Ovarian Cancer Metastasis
title Novel Chimeric Poxvirus CF17 Improves Survival in a Murine Model of Intraperitoneal Ovarian Cancer Metastasis
title_full Novel Chimeric Poxvirus CF17 Improves Survival in a Murine Model of Intraperitoneal Ovarian Cancer Metastasis
title_fullStr Novel Chimeric Poxvirus CF17 Improves Survival in a Murine Model of Intraperitoneal Ovarian Cancer Metastasis
title_full_unstemmed Novel Chimeric Poxvirus CF17 Improves Survival in a Murine Model of Intraperitoneal Ovarian Cancer Metastasis
title_short Novel Chimeric Poxvirus CF17 Improves Survival in a Murine Model of Intraperitoneal Ovarian Cancer Metastasis
title_sort novel chimeric poxvirus cf17 improves survival in a murine model of intraperitoneal ovarian cancer metastasis
topic Original Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7672245/
https://www.ncbi.nlm.nih.gov/pubmed/33251335
http://dx.doi.org/10.1016/j.omto.2020.10.002
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