Newswise — WASHINGTON, D.C. (May 3, 2015) — Winner of the Donald O. Quest Basic Science Award, Kushal Shah, MD, presented his research, Targeting Ezh2+ Cells with an Oncolytic Virus in Treatment of Glioma, during the 2015 American Association of Neurological Surgeons Annual Scientific Meeting.
The results of this study show that glioma cells are responsive to the SS3 virus in vitro and in vivo. The SS3 virus may play a role in the treatment of glioma, and further studies are warranted.
As a member of polycomb group (PcG), Ezh2 (enhancer of zeste homologue 2) is overexpressed in brain tumors. There is a resulting silencing of promoters of tumor suppressor genes. Glioblastoma multiforme (GBM) stem cells have been shown to maintain their undifferentiated characteristic nature through overexpression of Ezh2. Researchers on this study designed a novel oncolytic virus named Signal Smart 3 (SS3), which targets Ezh2+ cells.
There are many cell lines commercially available that mimic glioma. Proliferation assays and invasion assays were performed using the SS3 virus on these cell lines. Subcutaneous models in athymic nude mice with U87 cells (expressing luciferase) were used to test therapeutic intratumoral injection versus placebo injection. Intracranial model with U87 cells was tested with intratumoral injection versus placebo injection.
U251 stem cells express a significantly higher level of Ezh2 (1.63±0.04 ng/ml), compared to non-stem cells (1.05±0.07 ng/ml) (p=0.009). Proliferation assays showed a significant reduction in growth after two or three days post-infection with SS3 in glioma cells. Invasion assays on U118 and U251 showed reduction to 42.3±25.7 (p=0.05) and 22.9±13.3 (p=0.001) percent of control, respectively. The subcutaneous mouse model comparing therapeutic versus placebo showed a 75-percent reduction in tumor size, once the tumors were intratumorally injected with SS3 (6 injections). Intracranial model showed smaller tumor mass (1/3 of control) with two single intracranial injections of the virus.
Author Block: Warner Peng, MD; Brandon Ricke; Paul Camarata, MD, FAANS; Paul Arnold, MD, FAANS; Darren Lovick, MD, FAANS; Mike Salacz, MD; Faris Farassati, PharmD, PhD.
Disclosure: The author reported no conflicts of interest.
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