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Updated: Jun 18, 2026
An Orthotopic Model of Serous Ovarian Cancer in Immunocompetent Mice for in vivo Tumor Imaging and Monitoring of Tumor Immune Responses
Published on: November 28, 2010
Explicit targeting of transformed cells by VSV in ovarian epithelial tumor-bearing Wv mouse models
Callinice D Capo-chichi1, Toni M Yeasky, Joshua F Heiber
1Sylvester Comprehensive Cancer Center, University of Miami School of Medicine, Miami, FL 33136, USA.
Objective:
Current treatment options for epithelial ovarian cancer are limited and therapeutic development for recurrent and drug-resistant ovarian cancer is an urgent agenda. We investigated the potential use of genetically engineered Vesicular Stomatitis Virus (VSV) to treat ovarian cancer patients who fail to respond to available therapies. Specifically, we examined the toxicity to hosts and specificity of targeting ovarian tumors using a Wv ovarian tumor model.
Methods:
We first tested recombinant VSV for oncolytic activity in a panel of human ovarian epithelial cancer, immortalized, and primary ovarian surface epithelial cells in culture. Then, we tested VSV oncolytic therapy using the immune competent Wv mice that develop tubular adenomas, benign tumor lesions derived from ovarian surface epithelial cells.
Results:
The expression of GFP encoded by the recombinant VSV genome was detected in about 5% of primary ovarian surface epithelial cells (3 lines) up to 30 days without significantly altering the growth pattern of the cells, suggesting the lack of toxicity to the normal ovarian surface epithelial cells. However, VSV-GFP was detected in the majority (around 90%) of cells that are either "immortalized" by SV40 antigen expression or cancer lines. Some variation in killing time courses was observed, but all the transformed cell lines were killed within 3 days. We found that regardless of the inoculation route (intra bursal, IP, or IV), VSV specifically infected and replicated in the in situ ovarian tumors in the Wv mice without significant activity in any other organs and tissues, and showed no detectable toxicity. The epithelial tumor lesions were greatly reduced in VSV-targeted ovarian tumors in the Wv mice.
Conclusions:
VSV oncolytic activity depends on a cell autonomous property distinguishing primary and transformed cells. The efficient oncolytic activity of VSV for the "immortalized" non-tumorigenic ovarian surface epithelial cells suggests that the selective specificity extends from pre-neoplastic to overt cancer cells. The results demonstrated the explicit targeting of ovarian epithelial tumors by VSV in immune competent, ovarian tumor-bearing mouse models, and further support the utility of VSV as an effective and safe anti-cancer agent.
Insights
Genetically engineered Vesicular Stomatitis Virus (VSV) effectively targets and reduces ovarian tumors in mice, showing promise as a safe, novel cancer therapy for drug-resistant ovarian cancer.
Area of Science:
- Oncology
- Virology
- Biotechnology
Background:
- Epithelial ovarian cancer treatments are limited, especially for recurrent and drug-resistant cases.
- Novel therapeutic strategies are urgently needed for advanced ovarian cancer.
- Genetically engineered viruses offer a potential new avenue for cancer treatment.
Purpose of the Study:
- To investigate the potential of Vesicular Stomatitis Virus (VSV) as an oncolytic agent for ovarian cancer.
- To evaluate the safety and tumor-targeting specificity of VSV in an ovarian cancer model.
- To assess VSV's efficacy against both normal and cancerous ovarian epithelial cells.
Main Methods:
- Recombinant VSV expressing GFP was tested for oncolytic activity in human ovarian epithelial cells in vitro.
- VSV oncolytic therapy was evaluated in immune-competent Wv mice with ovarian tumors.
- Tumor targeting, viral replication, and host toxicity were assessed across different inoculation routes.
Main Results:
- VSV showed no significant toxicity to normal ovarian surface epithelial cells.
- VSV efficiently infected and killed immortalized and cancerous ovarian cell lines within 3 days.
- In vivo studies demonstrated VSV specifically targeted ovarian tumors in Wv mice without affecting other organs, significantly reducing tumor lesions.
Conclusions:
- VSV exhibits selective oncolytic activity against transformed ovarian cells, including pre-neoplastic and cancerous ones.
- VSV demonstrates explicit targeting of ovarian epithelial tumors in a relevant mouse model.
- VSV shows potential as an effective and safe anti-cancer agent for ovarian cancer treatment.
