Molecular Therapy: Oncolytics (Sep 2020)

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

  • 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

Journal volume & issue
Vol. 18
pp. 546 – 555

Abstract

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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.

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