title: Myxoma virus sensitizes cancer cells to gemcitabine and is an effective oncolytic virotherapeutic in models of disseminated pancreatic cancer.
abstract: Myxoma virus (MYXV) is a novel oncolytic virus that has been shown to replicate in pancreatic cancer cells, but its efficacy in animal models of pancreatic cancer has not been determined. The efficacy of MYXV as monotherapy or in combination with gemcitabine was evaluated in intraperitoneal dissemination (IPD) models of pancreatic cancer. The effects of an intact immune system on the efficacy of MYXV therapy was tested by comparing immunodeficient versus immunocompetent murine models and combination therapy with gemcitabine was also evaluated. In cell culture, MYXV replication was robust in a broad range of pancreatic cancer cells and also showed increased oncolysis in combination with gemcitabine. In animal models, MYXV treatment conferred survival benefits over control or gemcitabine-treated cohorts regardless of the cell line or animal model used. MYXV monotherapy was most effective in an immunocompetent IPD model, and resulted in 60% long-term survivors. In Pan02 engrafted immunocompetent IPD models, sequential treatment in which MYXV was administered first, followed by gemcitabine, was the most effective and resulted in 100% long-term survivors. MYXV is an effective oncolytic virus for pancreatic cancer and can be combined with gemcitabine to enhance survival, particularly in the presence of an intact host immune system.
authors.affiliation: Department of Molecular Genetics and Microbiology, University of Florida, Gainesville, Florida 32610, USA.
authors.forename: Sonia Tusell
authors.initials: ST
authors.lastname: Wennier
authors.forename: Jia
authors.initials: J
authors.lastname: Liu
authors.forename: Shoudong
authors.initials: S
authors.lastname: Li
authors.forename: Masmudur M
authors.initials: MM
authors.lastname: Rahman
authors.forename: Mahmoud
authors.initials: M
authors.lastname: Mona
authors.forename: Grant
authors.initials: G
authors.lastname: McFadden
mesh_terms: D000818:Animals; D000964:Antimetabolites, Antineoplastic / Q000627:therapeutic use*; D045744:Cell Line, Tumor; D002470:Cell Survival; D003841:Deoxycytidine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D008163:Luminescent Measurements; D051379:Mice; D008819:Mice, Nude; D008856:Microscopy, Fluorescence; D009233:Myxoma virus / Q000235:genetics / Q000502:physiology*; D050504:Oncolytic Viruses / Q000235:genetics / Q000502:physiology*; D010190:Pancreatic Neoplasms / Q000188:drug therapy* / Q000628:therapy*; D023041:Xenograft Model Antitumor Assays; D000093542:Gemcitabine
chemical_list: D000964:Antimetabolites, Antineoplastic; D003841:Deoxycytidine; D000093542:Gemcitabine