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Myxoma Virus Is Oncolytic for Human Pancreatic Adenocarcinoma Cells

¹ Department of Surgery, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York, NY 10065, USA
² Molecular Genetics and Microbiology, University of Florida, Gainesville, FL, USA
³ Biotherapeutics Research Group, Robarts Research Institute, and Department of Microbiology and Immunology, University of Western Ontario, Oshawa, ON, Canada

Correspondence: Address correspondence and reprint requests to: Yuman Fong, MD; E-mail: fongy{at}mskcc.org

Background: Viral oncolytic therapy, which seeks to exploit the use of live viruses to treat cancer, has shown promise in the treatment of cancers resistant to conventional anticancer therapies. Among the most difficult to treat cancers is advanced pancreatic adenocarcinoma. Our study investigates the ability of a novel oncolytic agent, myxoma virus, to infect, productively replicate in, and kill human pancreatic cancer cells in vitro.

Methods: The myxoma virus vMyxgfp was tested against a panel of human pancreatic adenocarcinoma cell lines. Infectivity, viral proliferation, and tumor cell kill were assessed.

Results: Infection of tumor cells was assessed by expression of the marker gene enhanced green fluorescent protein (e-GFP). vMyxgfp had the ability to infect all pancreatic cancer cell lines tested. Killing of tumor cells varied among the 6 cell lines tested, ranging from >90% cell kill at 7 days for the most sensitive Panc-1 cells, to 39% in the most resistant cell line Capan-2. Sensitivity correlated to replication of virus, and was found to maximally exhibit a four-log increase in foci-forming units for the most sensitive Panc-1 cells within 72 h.

Conclusion: Our study demonstrates for the first time the ability of the myxoma virus to productively infect, replicate in, and lyse human pancreatic adenocarcinoma cells in vitro. These data encourage further investigation of this virus, which is pathogenic only in rabbits, for treatment of this nearly uniformly fatal cancer.

Key Words: Oncolytic therapy • Myxoma virus • Viral vectors • Pancreatic cancer • In vitro