The overarching goal of this project is to identify a new lead oncolytic virus for the treatment of adult glioblastoma (GBM). Oncolytic viral (OV) therapy is a promising biological therapy that preferentially targets tumor cells for lytic destruction [1, 2]. Oncolytic HSV-1 (oHSV) derived virus that encodes for GM-CSF (IMLYGIC) has been recently approved for non-ressectable metastatic melanoma [3, 4]. In our past endeavors, we have created and tested the therapeutic efficacy of oHSV armed with therapeutic transgenes. These viruses have been created in rHSVQ1 (HSVQ): an HSV virus backbone that is deleted for both copies of the viral neuro- virulence gene ICP34.5 and it contains a gene disrupting insertion in viral ICP6. This backbone has attenuations identical to G207, a virus that has been tested and found to be safe in patients with GBM after intracranial inoculation into the tumor or when given into the post resection tumor cavity [5, 7-10]. Here we will create a novel dually armed oncolytic virus (that encode for therapeutic transgenes: Vstat120, PTEN? or both) and then compare the dually armed and single transgene armed viruses to identify an optimal vector for future IND guided studies.
The prognosis for GBM patients remains dismal and there is an urgent unmet need for novel therapies. The first oncolytic virus to be approved by the FDA is an oncolytic HSV whose use is prescribed for melanoma patients. To increase the utility of this novel approach for brain tumor patients we propose to create and optimize a lead HSV derived virus for development for clinical use.