Antitumor Efficacy of 34.5ENVE: A Transcriptionally Retargeted and "Vstat120"-expressing Oncolytic Virus

作者：Yoo Ji Young; Haseley Amy; Bratasz Anna; Chiocca E Antonio; Zhang Jianying; Powell Kimerly; Kaur Balveen^*

来源：Molecular Therapy, 2012, 20(2): 287-297.

DOI：10.1038/mt.2011.208

Here, we describe the construction and testing of a novel herpes simplex virus type 1 (HSV-1) derived oncolytic virus (OV): 34.5 ENVE (viral ICP34.5 Expressed by Nestin promotor and Vstat 120 Expressing), for the treatment of cancer. This virus showed significant glioma-specific killing and antiangiogenic effects in vitro and in vivo. Treatment of subcutaneous and intracranial glioma-bearing mice with 34.5ENVE showed a significant increase in median survival of mice in four different glioma models. Histology and dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) revealed reduced microvessel density (MVD) and increased tumoral necrosis in 34.5ENVE-treated tumor tissue compared to control OV-treated tumor tissue. Collectively, these results describe the construction, efficacy, and impact on tumor microenvironment of a transcriptionally driven OV armed with Vstat120 gene expression. These preclinical results will facilitate future clinical testing of 34.5ENVE.

• 出版日期2012-2