Oncolytic Virus with Attributes of Vesicular Stomatitis Virus and Measles Virus in Hepatobiliary and Pancreatic Cancers

• Main Authors: Bolni Marius Nagalo, Camilo Ayala Breton, Yumei Zhou, Mansi Arora, James M. Bogenberger, Oumar Barro, Michael B. Steele, Nathan J. Jenks, Alexander T. Baker, Dan G. Duda, Lewis Rowland Roberts, Stephen J. Russell, Kah Whye Peng, Mitesh J. Borad
• Format: Article
• Language: English
• Published: Elsevier 2020-09-01
• Series: Molecular Therapy: Oncolytics
• Subjects: hepatobiliary cancer; measles virus; oncolytic viral therapy; pancreatic cancer; vesicular stomatitis virus; hepatocellular carcinoma
• Online Access: http://www.sciencedirect.com/science/article/pii/S2372770520301248

Recombinant vesicular stomatitis virus (VSV)-fusion and hemagglutinin (FH) was developed by substituting the promiscuous VSV-G glycoprotein (G) gene in the backbone of VSV with genes encoding for the measles virus envelope proteins F and H. Hybrid VSV-FH exhibited a multifaceted mechanism of cancer-cell killing and improved neurotolerability over parental VSV in preclinical studies. In this study, we evaluated VSV-FH in vitro and in vivo in models of hepatobiliary and pancreatic cancers. Our results indicate that high intrahepatic doses of VSV-FH did not result in any significant toxicity and were well tolerated by transgenic mice expressing the measles virus receptor CD46. Furthermore, a single intratumoral treatment with VSV-FH yielded improved survival and complete tumor regressions in a proportion of mice in the Hep3B hepatocellular carcinoma model but not in mice xenografted with BxPC-3 pancreatic cancer cells. Our preliminary findings indicate that VSV-FH can induce potent oncolysis in hepatocellular and pancreatic cancer cell lines with concordant results in vivo in hepatocellular cancer and discordant in pancreatic cancer without the VSV-mediated toxic effects previously observed in laboratory animals. Further study of VSV-FH as an oncolytic virotherapy is warranted in hepatocellular carcinoma and pancreatic cancer to understand broader applicability and mechanisms of sensitivity and resistance.