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...
| Main Authors: | , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2020-12-01
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| Series: | Molecular Therapy: Oncolytics |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2372770520301534 |
| _version_ | 1818952740524523520 |
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| author | Mohamed Hammad Yvonne Cornejo Linda Flores Caitlyn Hyde Hoi Wa Ngai Min Li Thanh H. Dellinger Jianming Lu Nanhai G. Chen Rachael Mooney Karen S. Aboody Yuman Fong |
| author_facet | Mohamed Hammad Yvonne Cornejo Linda Flores Caitlyn Hyde Hoi Wa Ngai Min Li Thanh H. Dellinger Jianming Lu Nanhai G. Chen Rachael Mooney Karen S. Aboody Yuman Fong |
| author_sort | Mohamed Hammad |
| collection | DOAJ |
| 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 × 106 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. |
| first_indexed | 2024-12-20T09:55:11Z |
| format | Article |
| id | doaj.art-e66a68f7680d47709c841521226bf217 |
| institution | Directory Open Access Journal |
| issn | 2372-7705 |
| language | English |
| last_indexed | 2024-12-20T09:55:11Z |
| publishDate | 2020-12-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Molecular Therapy: Oncolytics |
| spelling | doaj.art-e66a68f7680d47709c841521226bf2172022-12-21T19:44:29ZengElsevierMolecular Therapy: Oncolytics2372-77052020-12-0119278282Novel Chimeric Poxvirus CF17 Improves Survival in a Murine Model of Intraperitoneal Ovarian Cancer MetastasisMohamed Hammad0Yvonne Cornejo1Linda Flores2Caitlyn Hyde3Hoi Wa Ngai4Min Li5Thanh H. Dellinger6Jianming Lu7Nanhai G. Chen8Rachael Mooney9Karen S. Aboody10Yuman Fong11Department of Stem Cell and Developmental Biology, City of Hope, Duarte, CA 91010, USA; Corresponding author: Mohamed Hammad, Department of Stem Cell and Developmental Biology, City of Hope, Duarte, CA 91010, USA.Department of Stem Cell and Developmental Biology, City of Hope, Duarte, CA 91010, USA; Irell & Manella Graduate School for Biological Sciences, Beckman Research Institute, City of Hope, Duarte, CA 91010, USADepartment of Stem Cell and Developmental Biology, City of Hope, Duarte, CA 91010, USADepartment of Stem Cell and Developmental Biology, City of Hope, Duarte, CA 91010, USADepartment of Stem Cell and Developmental Biology, City of Hope, Duarte, CA 91010, USADepartment of Information Sciences, Division of Biostatistics at the Beckman Research Institute, City of Hope, Duarte, CA 91010, USADivision of Gynecologic Surgery, Department of Surgery, City of Hope, Duarte, CA 91010, USAIrell & Manella Graduate School for Biological Sciences, Beckman Research Institute, City of Hope, Duarte, CA 91010, USADepartment of Surgery, City of Hope, Duarte, CA 91010, USA; Center for Gene Therapy, City of Hope, Duarte, CA 91010, USADepartment of Stem Cell and Developmental Biology, City of Hope, Duarte, CA 91010, USADepartment of Stem Cell and Developmental Biology, City of Hope, Duarte, CA 91010, USA; Division of Neurosurgery, City of Hope, Duarte, CA 91010, USADepartment of Surgery, City of Hope, Duarte, CA 91010, USA; Center for Gene Therapy, City of Hope, Duarte, CA 91010, USADespite 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 × 106 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.http://www.sciencedirect.com/science/article/pii/S2372770520301534oncolytic virotherapychimeric poxvirusovarian cancer |
| spellingShingle | Mohamed Hammad Yvonne Cornejo Linda Flores Caitlyn Hyde Hoi Wa Ngai Min Li Thanh H. Dellinger Jianming Lu Nanhai G. Chen Rachael Mooney Karen S. Aboody Yuman Fong Novel Chimeric Poxvirus CF17 Improves Survival in a Murine Model of Intraperitoneal Ovarian Cancer Metastasis Molecular Therapy: Oncolytics oncolytic virotherapy chimeric poxvirus ovarian cancer |
| 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 | oncolytic virotherapy chimeric poxvirus ovarian cancer |
| url | http://www.sciencedirect.com/science/article/pii/S2372770520301534 |
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