A Fusogenic Oncolytic Herpes Simplex Virus for Therapy of Advanced Ovarian Cancer
Abstract
The safety of the first generation oncolytic HSVs (e.g., G2O7) has been well documented and are currently in clinical trials. However, the available evidence so far indicates that, although safe, they may have only limited antitumor activity on their own. We have demonstrated that a doubly fusogenic oncolytic HSV, Synco-2D, is extremely effective at destroying metastatic ovarian cancer. However, maintaining the safety profile of the first generation oncolytic HSVs is mandatory for the potential application of Synco-2D in the clinics. We therefore devoted the second year of this project to evaluate the toxicity of Synco-2D. Our results show that: 1) Direct injection of the virus to the CNS at a relatively large dose did not cause any mortality. 2) Systemic administration of oncolytic HSVs caused a mild liver abnormity as identified by histological examination. However, there was no significant difference on the severity of liver toxicity between the doubly fusogenic and the nonfusogenic oncolytic HSVs. This mild liver toxicity is most likely due to the preferred deposit of the systemically delivered viruses to this organ. Virus titration did not detect any residual infectious virus from other major organs. Together, these results confirm our original hypothesis that due to the unique design of the doubly fusogenic Synco-2D, it is not significantly more toxic than the nonfusogenic counterpart despite its dramatically enhanced antitumor activity.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jun 01, 2005
- Accession Number
- ADA444233
Entities
People
- Xiaoliu Zhang
Organizations
- Baylor College of Medicine