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

Research output: Contribution to journalArticlepeer-review

1 Scopus citations

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-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.

Original languageEnglish (US)
Pages (from-to)546-555
Number of pages10
JournalMolecular Therapy - Oncolytics
Volume18
DOIs
StatePublished - Sep 25 2020

Keywords

  • cholangiocarcinoma
  • hepatobiliary cancer
  • hepatocellular carcinoma
  • measles virus
  • oncolytic viral therapy
  • pancreatic cancer
  • vesicular stomatitis virus

ASJC Scopus subject areas

  • Molecular Medicine
  • Oncology
  • Cancer Research
  • Pharmacology (medical)

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