Construction of a Vesicular Stomatitis virus Expressing Both a Fusogenic Glycoprotein and IL-12: A Novel Vector for Prostate Cancer Therapy

摘要

Introduction: Vesicular Stomatitis Virus (VSV) infection of malignant cells results in oncolysis, sparing normal cells due to inherent differences in the interferon response pathway. In this study we explored enhancing VSV-G by engineering it to express the fusogenic glycoprotein from the Newcastle Disease Virus (VSV-F) to induce inter-cellular membrane fusion producing syncytia, which are incompatible with cell survival. Materials and Methods: Studies initially compared effects of VSV and VSV-F in vitro in prostate cancer cells lines, noting differential effects at different cell densities and the induction of apoptosis. Studies then compared effects of VSV vs VSV-F in a orthoptic mouse model of prostate cancer, focusing on tumor size at set time points and survival. Results: As the confluence of cells in the wells became greater, VSV-F showed more rapid cell kill than VSV-G.