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Abstract Title:

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

Abstract Source:

Mol Ther Oncolytics. 2020 Sep 25 ;18:546-555. Epub 2020 Aug 19. PMID: 32839735

Abstract Author(s):

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

Article Affiliation:

Bolni Marius Nagalo

Abstract:

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-FHandin 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 resultsin 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.

Study Type : In Vitro Study

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