Fusogenic Oncolytic Herpes Simplex Virus for Therapy of Advanced Ovarian Cancer

摘要

The underlying hypothesis for this project is that incorporation of cell membrane fusion function into an oncolytic herpes simplex virus (HSV) can significantly enhance the anti-tumor effect of the virus. Three specific aims have been proposed and they are: (1) to demonstrate that fusogenic oncolytic HSVs are a potent anti-tumor agent for advanced ovarian cancer; (2) to prove that fusogenic oncolytic HSVs have the same safety profile as their non- fusogenic counterparts; (3) to explore novel delivery strategies that can evade host s anti-viral immunity for repeated delivery. During the funding period, these aims have been mostly achieved. Our data show that incorporation of a fusogenic glycoprotein (GALV.fus) into an oncolytic herpes simplex virus through a novel controlling mechanism can significantly enhance the antitumor potency of the virus without significantly increasing its toxicity. In the efforts to identify a strategy that can deliver an oncolytic HSV to tumor tissues systemically in the presence of host s antiviral immunity, we demonstrate that delivery of an oncolytic HSV as a DNA form rather the traditional viral particles represents a possibility. We also show that blood cells such as monocytes/macrophages from STAT1-deficient background could function as cell carriers for systemic delivery of these oncolytic viruses. Several publications have been produced during the funding period. One of the oncolytic viruses that were studied during the funding period is currently being evaluated for translation into clinical testing for treating solid tumors including ovarian cancer.