A Fusogenic Oncolytic Herpes Simplex Virus for Therapy of Advanced Ovarian Cancer
Abstract
For efficient therapy of solid tumors such as ovarian cancer, two obstacles need to be overcome before the therapeutic potential of virotherapy could be fully materialized. Firstly, the potency of oncolytic HSVs needs to be improved. During the first two years of this funded project, we have demonstrated that incorporation of cell-membrane fusion activity into an oncolytic HSV could significantly and safely increase the antitumor potency of the virus. Secondly, host's antiviral immunity is likely to be a major obstacle for successful administration of an oncolytic virus. We proposed in the third year of this project to develop strategies to overcome this potential problem. Our hypothesis is that the ability of a fusogenic oncolytic HSV to induce cell membrane fusion would make the virus less vulnerable to the innate and/or acquired antiviral immunity once it had entered to the tumor cells, as it would be able to spread from cell to cell through syncytia formation. Thus, a strategy that could initially send the virus to the tumor site in the presence of host's antiviral immunity would be what was needed to overcome the initial hurdle of its delivery. Our data demonstrated that: 1) the fusogenic oncolytic HSVs have the ability to spread to surrounding tumor cells even in the presence of high concentration of antiviral immune sera, indicating its ability to evade the host's neutralizing antibodies once the virus has entered into the target cells; 2) an HSV-2-based fusogenic oncolytic HSV (Fusion-H2) has the ability to evade the host s innate antiviral immunity; 3) oncolytic HSVs could be formulated with liposomes for in vivo delivery; 4) in addition to T lymphocytes, NK cells and macrophages could also function as carrier cells for delivery of oncolytic HSVs by the recently reported hitchhike strategy. This represent a very efficient way of loading oncolytic virus to the carrier cells, which are otherwise nonpermissiveness to infection of oncolytic HSVs.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jun 01, 2006
- Accession Number
- ADA462400
Entities
People
- Xiaoliu Zhang
Organizations
- Baylor College of Medicine