OvAd1, a Novel, Potent, and Selective Chimeric Oncolytic Virus Developed for Ovarian Cancer by 3D-Directed Evolution

Kuhn, Irene; Bauzon, Maxine; Green, Nicola; Seymour, Len; Fisher, Kerry; Hermiston, Terry

doi:10.1016/j.omto.2016.12.001

Title: OvAd1, a Novel, Potent, and Selective Chimeric Oncolytic Virus Developed for Ovarian Cancer by 3D-Directed Evolution

Journal Article · Thu Dec 15 00:00:00 EST 2016 · Molecular Therapy Oncolytics

DOI:https://doi.org/10.1016/j.omto.2016.12.001· OSTI ID:1623710

Kuhn, Irene ^[1]; Bauzon, Maxine ^[2]; Green, Nicola ^[3]; Seymour, Len ^[3]; Fisher, Kerry ^[3]; Hermiston, Terry ^[2]

Bayer Pharmaceuticals, San Francisco, CA (United States); Lawrence Berkeley National Laboratory (LBNL), Berkeley, CA (United States)
Bayer Pharmaceuticals, San Francisco, CA (United States)
University of Oxford (United Kingdom)

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-Matrigelderived 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.

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Research Organization:: Lawrence Berkeley National Laboratory (LBNL), Berkeley, CA (United States)

Sponsoring Organization:: USDOE Office of Science (SC), Biological and Environmental Research (BER). Biological Systems Science Division; Cancer Research UK

Grant/Contract Number:: AC02-05CH11231; C552/A17720

OSTI ID:: 1623710

Journal Information:: Molecular Therapy Oncolytics, Vol. 4, Issue C; ISSN 2372-7705

Publisher:: ElsevierCopyright Statement

Country of Publication:: United States

Language:: English

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59 BASIC BIOLOGICAL SCIENCES
60 APPLIED LIFE SCIENCES
3D cell culture
Matrigel
oncolytic
virotherapy
ovarian cancer
directed evolution
adenovirus
replicating

Title: OvAd1, a Novel, Potent, and Selective Chimeric Oncolytic Virus Developed for Ovarian Cancer by 3D-Directed Evolution

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