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Myxoma Virus Is Oncolytic for Human Pancreatic Adenocarcinoma Cells
Authors:Yanghee Woo MD  Kaitlyn J Kelly MD  Marianne M Stanford PhD  Charles Galanis MD  Yun Shin Chun MD  Yuman Fong MD  Grant McFadden PhD
Institution:(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
Abstract: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.
Keywords:Oncolytic therapy  Myxoma virus  Viral vectors  Pancreatic cancer  In vitro
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