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Oncolytic Virus Therapy in Combination with Chemotherapy for Ovarian Cancer.

Bolyard, Chelsea M
http://rave.ohiolink.edu/etdc/view?acc_num=osu1386007453

Abstract Details

2013, Doctor of Philosophy, Ohio State University, Integrated Biomedical Science Graduate Program.
Purpose. Novel therapeutic regimens are needed to improve dismal outcomes associated with late-stage ovarian cancer. Oncolytic viruses have shown efficacy against ovarian cancer. We studied the application of an oncolytic herpes simplex virus expressing two anti-tumor genes: ICP34.5 under the stem cell-specific nestin promoter, and anti-angiogenic molecule Brain-specific Angiogenesis Inhibitor-1 (BAI1) under the strong viral promoter IE4/5 for use against ovarian cancer. We also studied the use of this viral vector in combination with a second-line standard of care chemotherapeutic drug, doxorubicin. Experimental Design. The 34.5 Expressing Nestin-driven Vasculostatin-120 Expressing (34.5ENVE) virus was tested for treatment of ovarian cancer in vitro and in vivo. Efficacy of the virus, and its antiangiogenic effects on endothelial cells were assessed in vitro in cancer cell lines and in primary patient ascites samples. Scope of cytotoxic interactions between 34.5ENVE and chemotherapeutic agent doxorubicin were evaluated using Chou-Talalay synergy analysis. Efficacy of oncolytic viral therapy in combination with doxorubicin was evaluated in vivo in the murine xenograft model of progressive human ovarian cancer. Results. 34.5ENVE showed robust efficacy against ovarian cancer cell lines, and even greater efficacy against ex vivo mouse and patient ascites. When combined with doxorubicin, 34.5ENVE killed synergistically with a robust increase in caspase-3/7 cleavage. The combination of doxorubicin and 34.5ENVE significantly prolonged survival in nude mice bearing intraperitoneal ovarian cancer tumors. Conclusions. This study establishes the potential for use of oncolytic HSV in combination with doxorubicin for the treatment of late-stage ovarian cancer.
Balveen Kaur, PhD (Advisor)
Douglas McCarty, PhD (Committee Chair)
Robert Munson, PhD (Committee Member)
Pravin Kaumaya, Jr., PhD (Committee Member)
174 p.
Biomedical Research
oncolytic virus, herpes simplex virus, ovarian cancer, doxorubicin, synergy

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Citations

  • Bolyard, C. M. (2013). Oncolytic Virus Therapy in Combination with Chemotherapy for Ovarian Cancer. [Doctoral dissertation, Ohio State University]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=osu1386007453

    APA Style (7th edition)

  • Bolyard, Chelsea. Oncolytic Virus Therapy in Combination with Chemotherapy for Ovarian Cancer. . 2013. Ohio State University, Doctoral dissertation. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=osu1386007453.

    MLA Style (8th edition)

  • Bolyard, Chelsea. "Oncolytic Virus Therapy in Combination with Chemotherapy for Ovarian Cancer. ." Doctoral dissertation, Ohio State University, 2013. http://rave.ohiolink.edu/etdc/view?acc_num=osu1386007453

    Chicago Manual of Style (17th edition)

osu1386007453
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© 2013, all rights reserved.
This open access ETD is published by The Ohio State University and OhioLINK.