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- Title
772. Inhibition of Ovarian Tumor Growth Following Treatment with an Oncolytic Vaccinia Virus.
- Authors
Xiang Da (Eric) Dong; O'Malley, Mark E.; Chalikonda1, Sri; Zongsheng Guo; Zeh, Herbert J.; Bartlett, David L.
- Abstract
Background: Recombinant vaccinia virus is currently being explored as a potential replicating oncolytic virus for cancer virotherapy due to its exceptional ability to replicate in tumor cells. Vaccinia tropism is not limited to tumor tissues, but also other tissues including ovarian follicles, possibly due to the presence of angiogenic factors such as vascular endothelial growth factor (VEGF). We therefore investigated the utility of vaccinia virus as an oncolytic therapy in a murine model of ovarian cancer.Methods: A murine ovarian surface epithelial cell (MOSEC) line was employed for this model. Intraperitoneal inoculation of the MOSEC cell line leads to a highly malignant neoplasm containing both carcinomatous and sarcomatous components as well as production of hemorrhagic ascitic fluid. These mice were treated with a thymidine kinase (TK) and vaccinia growth factor (VGF) double-deleted virus with the cytokine deaminase (CD) gene inserted into the TK locus. This recombinant virus (vvddCD) was found to be equivalent to the native WR strain in tumor tropism with minimal systemic growth.Results: Following intraperitoneal (i.p.) inoculation with 7.5x106 cells, mice were treated with 109 pfu of the vvddCD strain of vaccinia virus i.p. on the same day (concurrent treatment). In vivo studies appeared to show complete inhibition of tumor growth as compared to the control group (median mouse weight with ascites at 88 days: 40.7+/-1.49 (control [n=10]) vs 27.43+/-1.12 (virus [n=10])) (p<0.01). Hemorrhagic ascites formation was completely abrogated through treatment with the virus. All untreated mice either died or were sacrificed due to overwhelming ascitic fluid burden by 94 days following tumor inoculation. Treatment with virus was able to prevent or delay establishment of tumor and/or ascitic fluid with all treated mice viable and healthy at 161 days. Delayed treatment strategies with injections of 109 pfu of vvddCD at thirty (30) or sixty (60) days post tumor cell inoculation again appeared to show significant inhibition of tumor growth compared to control. For the 30 day treatment group the median mouse weight with ascites at day 75 was 39.3+/-1.65 (control [n=10]) vs 29.87+/- 1.54 (virus [n=10])) (p<0.05). All control mice either died or were sacrificed by 88 days; for animals treated at 30 days, 90% were viable at 88 days. By day 105, 50% of the 30 day treatment group were still viable. For the 60 day treatment group, 50% of treated animals were viable at day 88. All animals in the 60 day treatment group died or were euthanized by day 125.Conclusions: Treatment with a double-deleted recombinant vaccinia virus has been demonstrated to either completely abrogate (concurrent treatment) or significantly inhibit (delayed treatment) tumor progression in a murine ovarian model. The therapeutic application of vaccinia vectors expressing recombinant gene products in ovarian cancer represents a potential avenue of use given its biological safety, tumor selectivity and oncolytic potential.Molecular Therapy (2006) 13, S298–S299; doi: 10.1016/j.ymthe.2006.08.858
- Subjects
CANCER treatment; OVARIAN tumors; CANCER invasiveness; TUMOR growth; CANCER cells; CELLULAR immunity
- Publication
Molecular Therapy, 2006, Vol 13, pS298
- ISSN
1525-0016
- Publication type
Article
- DOI
10.1016/j.ymthe.2006.08.858