An Oncolytic Herpes Simplex Virus Restricted in Entry to Neuroblastoma Cells
Neuroblastoma is the third most common cancer in children and the most common malignancy in infants. Although treatment options are improving, survival rates for newly diagnosed patients remain at around 70%. Metastatic disease at the time of diagnosis confers a poorer prognosis, and the 3-year survival rate for patients with recurrent disease is only around 30%.
The field of oncology has recently seen increased interest in the use of engineered viruses as treatments which selectively replicate within and kill tumor cells while sparing normal cells.
Our group has extensive experience with herpes simplex virus (HSV), which has characteristics favoring its use as a viral oncolytic therapy. In particular, HSV can be manipulated to restrict entry of the virus into cells which express specific proteins. We have created modified HSV viruses with entry restricted to use a protein known as GD2, which exists at high levels on the surface of neuroblastoma cells.
In this study, we propose to test these constructs in neuroblastoma cells and in animal models of neuroblastoma disease. We intend for these studies to be an initial proof-of-principle for oncolytic virotherapy directed toward a pediatric disease which is difficult to treat and is associated with a very high mortality rate.