Toxicity and Efficacy of a Novel GADD34-expressing Oncolytic HSV-1 for the Treatment of Experimental Glioblastoma.

ABSTRACT: Purpose: Glioblastoma (GBM) is the most common primary central nervous system cancer in adults. Oncolytic HSV-1 (oHSV) is the first FDA-approved gene therapy approach for the treatment of malignant melanoma. For GBM, oHSVs need to be engineered to replicate within and be toxic to the glial tumor but not to normal brain parenchymal cells. We have thus engineered a novel oHSV to achieve these objectives.Experimental Design: NG34 is an attenuated HSV-1 with deletions in the genes encoding viral ICP6 and ICP34.5. These mutations suppress virus replication in nondividing brain neurons. NG34 expresses the human GADD34 gene under transcriptional control of a cellular Nestin gene promoter/enhancer element, whose expression occurs selectively in GBM. In vitro cytotoxicit

SUBMITTER: Nakashima H 

PROVIDER: S-EPMC6800093 | biostudies-literature | 2018 Jun

REPOSITORIES: biostudies-literature