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Updated: Aug 30, 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
Oncolytic viral therapy for human ovarian cancer using a novel replication-competent herpes simplex virus type I
Akihiro Nawa1, Naoki Nozawa, Fumi Goshima
1Department of Gynecology, Aichi Cancer Center Hospital, 1-1 kanokoden, Chikusa-ku, Nagoya, 464-8681, Japan. nawa2000@aichi-cc.jp
Objective:
Attenuated mutant strains of herpes simplex virus (HSV) have been effectively used for treatment of malignant brain tumors. As HSV-1 can infect and lyse a variety of cell types, other malignancies may also benefit from such treatment. We sought to test the feasibility of HSV-1 mutant-mediated gene therapy treatment of ovarian cancer.
Methods:
We prepared two attenuated mutant HSV-1 strains. An HSV-1 mutant, hrR3, has replaced the gene encoding ribonucleotide reductase (RR) with the lacZ reporter gene. We also developed a new replication-competent HSV-1 mutant, HR522; this virus, expressing the lacZ reporter gene, induces syncytium formation in infected cells. We compared the efficacy of HR522 with, paclitaxel (Taxol) and hrR3 in the treatment of nude mice harboring human ovarian cancer cells. We also examined the effect of the prodrug ganciclovir (GCV) on the treatment mediated by these HSVs. Survival was evaluated by Kaplan-Meier method and log-rank test.
Results:
The survival of mice treated with a high-titer hrR3 (5 x 10(7) plaque-forming units [PFU]) was significantly prolonged as compared with the group given paclitaxel (P < 0.0001, log-rank test). Although the survival of mice treated with high-titer HR522 (5 x 10(7) PFU) was not significantly prolonged compared with paclitaxel-treated group (P = 0.212, log-rank test), GCV markedly enhanced the efficacy of HR522 administration (P < 0.005, vs paclitaxel, log-rank test). The lacZ gene product, visualized using 5-bromo-4-chloro-3-indolyl-beta-D-galactopyranoside (X-gal) histochemistry, was detected in HR522-treated tumors in areas also exhibiting apoptotic changes.
Conclusions:
These findings indicate that the combination of HR522 and GCV possesses significant therapeutic potential for treatment of ovarian cancer. Such viral therapy offers a novel approach to reductions in the dissemination of ovarian cancer.
Insights
Herpes simplex virus-1 (HSV-1) mutant HR522 combined with ganciclovir (GCV) shows significant therapeutic potential for ovarian cancer treatment. This viral therapy offers a novel approach to reduce ovarian cancer spread.
Area of Science:
- Oncolytic virotherapy
- Gene therapy
- Herpes Simplex Virus (HSV) research
Background:
- Attenuated herpes simplex virus (HSV) strains are effective in treating malignant brain tumors.
- HSV-1's ability to infect and lyse various cell types suggests potential for treating other cancers.
- Ovarian cancer remains a significant health concern, necessitating novel therapeutic strategies.
Purpose of the Study:
- To evaluate the feasibility of using HSV-1 mutant-mediated gene therapy for ovarian cancer.
- To compare the efficacy of two attenuated HSV-1 mutant strains (hrR3 and HR522) against human ovarian cancer xenografts.
- To assess the impact of ganciclovir (GCV) on the therapeutic outcomes of HSV-1 treatment.
Main Methods:
- Two attenuated HSV-1 mutant strains were prepared: hrR3 (ribonucleotide reductase gene replaced with lacZ) and HR522 (replication-competent, expressing lacZ).
- Efficacy was compared in nude mice with human ovarian cancer xenografts, using HR522, hrR3, and paclitaxel (Taxol).
- The effect of ganciclovir (GCV) on HSV-mediated treatment was examined, with survival analyzed using Kaplan-Meier and log-rank tests.
Main Results:
- Mice treated with high-titer hrR3 showed significantly prolonged survival compared to paclitaxel (P < 0.0001).
- High-titer HR522 alone did not significantly prolong survival compared to paclitaxel (P = 0.212).
- Ganciclovir (GCV) markedly enhanced the efficacy of HR522, significantly improving survival compared to paclitaxel (P < 0.005).
- LacZ expression was detected in HR522-treated tumors, correlating with apoptotic changes.
Conclusions:
- The combination of HR522 and GCV demonstrates significant therapeutic potential for ovarian cancer.
- This oncolytic viral therapy presents a novel strategy for reducing ovarian cancer dissemination.
- Further research into HSV-based therapies for ovarian cancer is warranted.
