OvAd1, a novel, potent, and selective chimeric oncolytic virus developed for ovarian cancer by 3D-directed evolution
Effective therapeutics for ovarian cancer continue to be urgently needed, particularly for chemotherapy-resistant cases. Here we present both a 3D-Matrigel culture-based expansion of our directed evolution method for generation of oncolytic virotherapies and two promising ovarian-cancer targeted onc...
| Main Authors: | , , , , , |
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| Format: | Journal article |
| Language: | English |
| Published: |
Elsevier
2017
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| _version_ | 1826280481889452032 |
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| author | Kuhn, I Bauzon, M Green, N Seymour, L Fisher, K Hermiston, T |
| author_facet | Kuhn, I Bauzon, M Green, N Seymour, L Fisher, K Hermiston, T |
| author_sort | Kuhn, I |
| collection | OXFORD |
| description | Effective therapeutics for ovarian cancer continue to be urgently needed, particularly for chemotherapy-resistant cases. Here we present both a 3D-Matrigel culture-based expansion of our directed evolution method for generation of oncolytic virotherapies and two promising ovarian-cancer targeted oncolytic viruses, OvAd1 and OvAd2. OvAd1 was developed using Matrigel cell cultures, whereas OvAd2 was developed in parallel using traditional monolayer tissue culture methods. Both viruses are potent against a panel of platinum-resistant ovarian cancer cell lines and are attenuated on normal cells in vitro, resulting in therapeutic windows of ∼200-fold. We observed two benefits of the use of Matrigel-based cultures for directed evolution of these oncolytics: (1) use of Matrigel generated a bioselected pool that was more strongly attenuated on normal cells while retaining its potency against ovarian cancer cells, and (2) in an ovarian carcinomatosis model, the Matrigel-derived virus OvAd1 suppressed all tumor growth while the non-Matrigel-derived virus was 50% effective. Neither virus stimulated formation of peritoneal adhesions as seen for Ad5-based therapies. Consequently, these viruses are novel candidates for development as new effective treatments for aggressive ovarian cancer. |
| first_indexed | 2024-03-07T00:14:22Z |
| format | Journal article |
| id | oxford-uuid:7a50d6d9-bf16-4265-b050-ac7b754ac539 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-07T00:14:22Z |
| publishDate | 2017 |
| publisher | Elsevier |
| record_format | dspace |
| spelling | oxford-uuid:7a50d6d9-bf16-4265-b050-ac7b754ac5392022-03-26T20:43:13ZOvAd1, a novel, potent, and selective chimeric oncolytic virus developed for ovarian cancer by 3D-directed evolutionJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:7a50d6d9-bf16-4265-b050-ac7b754ac539EnglishSymplectic Elements at OxfordElsevier2017Kuhn, IBauzon, MGreen, NSeymour, LFisher, KHermiston, TEffective therapeutics for ovarian cancer continue to be urgently needed, particularly for chemotherapy-resistant cases. Here we present both a 3D-Matrigel culture-based expansion of our directed evolution method for generation of oncolytic virotherapies and two promising ovarian-cancer targeted oncolytic viruses, OvAd1 and OvAd2. OvAd1 was developed using Matrigel cell cultures, whereas OvAd2 was developed in parallel using traditional monolayer tissue culture methods. Both viruses are potent against a panel of platinum-resistant ovarian cancer cell lines and are attenuated on normal cells in vitro, resulting in therapeutic windows of ∼200-fold. We observed two benefits of the use of Matrigel-based cultures for directed evolution of these oncolytics: (1) use of Matrigel generated a bioselected pool that was more strongly attenuated on normal cells while retaining its potency against ovarian cancer cells, and (2) in an ovarian carcinomatosis model, the Matrigel-derived virus OvAd1 suppressed all tumor growth while the non-Matrigel-derived virus was 50% effective. Neither virus stimulated formation of peritoneal adhesions as seen for Ad5-based therapies. Consequently, these viruses are novel candidates for development as new effective treatments for aggressive ovarian cancer. |
| spellingShingle | Kuhn, I Bauzon, M Green, N Seymour, L Fisher, K Hermiston, T OvAd1, a novel, potent, and selective chimeric oncolytic virus developed for ovarian cancer by 3D-directed evolution |
| title | OvAd1, a novel, potent, and selective chimeric oncolytic virus developed for ovarian cancer by 3D-directed evolution |
| title_full | OvAd1, a novel, potent, and selective chimeric oncolytic virus developed for ovarian cancer by 3D-directed evolution |
| title_fullStr | OvAd1, a novel, potent, and selective chimeric oncolytic virus developed for ovarian cancer by 3D-directed evolution |
| title_full_unstemmed | OvAd1, a novel, potent, and selective chimeric oncolytic virus developed for ovarian cancer by 3D-directed evolution |
| title_short | OvAd1, a novel, potent, and selective chimeric oncolytic virus developed for ovarian cancer by 3D-directed evolution |
| title_sort | ovad1 a novel potent and selective chimeric oncolytic virus developed for ovarian cancer by 3d directed evolution |
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