title: Oncolytic gene therapy with recombinant vaccinia strain GLV-2b372 efficiently kills hepatocellular carcinoma.
abstract: BACKGROUND
  Hepatocellular carcinoma (HCC) commonly presents at a late stage when surgery is no longer a curative option. As such, novel therapies for advanced HCC are needed. Oncolytic viruses are a viable option for cancer therapy owing to their ability to specifically infect, replicate within, and kill cancer cells. In this study, we have investigated the ability of GLV-2b372, a novel light-emitting recombinant vaccinia virus derived from a wild-type Lister strain, to kill HCC.
  
  
  METHODS
  Four human HCC cell lines were assayed in vitro for infectivity and cytotoxicity. Viral replication was quantified via standard viral plaque assays. Flank HCC xenografts generated in athymic nude mice were treated with intratumoral GLV-2b372 to assess for tumor growth inhibition and viral biodistribution.
  
  
  RESULTS
  Infectivity occurred in a time- and concentration-dependent manner with 70% cell death in all cell lines by day 5. All cell lines supported efficient viral replication. At 25 days after infection, flank tumor volumes decreased by 50% whereas controls increased by 400%. Tumor tissue demonstrated substantial GLV-2b372 infection at 24 hours, 48 hours, and 2 weeks.
  
  
  CONCLUSIONS
  We demonstrate that GLV-2b372 efficiently kills human HCC in vitro and in vivo and is a viable treatment option for patients with HCC.
authors.affiliation: Department of Surgery, Memorial Sloan-Kettering Cancer Center, New York, NY.
authors.forename: Justin W
authors.initials: JW
authors.lastname: Ady
authors.affiliation: Department of Surgery, Memorial Sloan-Kettering Cancer Center, New York, NY.
authors.forename: Clark
authors.initials: C
authors.lastname: Johnsen
authors.affiliation: Department of Surgery, Memorial Sloan-Kettering Cancer Center, New York, NY.
authors.forename: Kelly
authors.initials: K
authors.lastname: Mojica
authors.affiliation: Department of Surgery, Memorial Sloan-Kettering Cancer Center, New York, NY.
authors.forename: Jacqueline
authors.initials: J
authors.lastname: Heffner
authors.affiliation: Department of Surgery, Memorial Sloan-Kettering Cancer Center, New York, NY.
authors.forename: Damon
authors.initials: D
authors.lastname: Love
authors.affiliation: Department of Surgery, Memorial Sloan-Kettering Cancer Center, New York, NY.
authors.forename: Amudhan
authors.initials: A
authors.lastname: Pugalenthi
authors.affiliation: Department of Surgery, Memorial Sloan-Kettering Cancer Center, New York, NY.
authors.forename: Laurence J
authors.initials: LJ
authors.lastname: Belin
authors.affiliation: Genelux Corporation, San Diego Science Center, San Diego, CA; Department of Radiation Medicine and Applied Sciences, Rebecca & John Moores Comprehensive Cancer Center, University of California, San Diego, CA.
authors.forename: Nanhai G
authors.initials: NG
authors.lastname: Chen
authors.affiliation: Genelux Corporation, San Diego Science Center, San Diego, CA.
authors.forename: Yong A
authors.initials: YA
authors.lastname: Yu
authors.affiliation: Genelux Corporation, San Diego Science Center, San Diego, CA; Department of Radiation Medicine and Applied Sciences, Rebecca & John Moores Comprehensive Cancer Center, University of California, San Diego, CA; Department of Biochemistry, Rudolph Virchow Center for Experimental Biomedicine, and Institute for Molecular Infection Biology, University of Würzburg, Würzburg, Germany.
authors.forename: Aladar A
authors.initials: AA
authors.lastname: Szalay
authors.affiliation: Department of Surgery, City of Hope Medical Center, Duarte, CA. Electronic address: yfong@COH.org.
authors.forename: Yuman
authors.initials: Y
authors.lastname: Fong
mesh_terms: D000818:Animals; D006528:Carcinoma, Hepatocellular / Q000628:therapy*; D045744:Cell Line, Tumor; D005260:Female; D015316:Genetic Therapy; D006801:Humans; D008113:Liver Neoplasms / Q000628:therapy*; D051379:Mice; D008819:Mice, Nude; D050130:Oncolytic Virotherapy; D050504:Oncolytic Viruses / Q000235:genetics*; D016896:Treatment Outcome; D014616:Vaccinia virus / Q000235:genetics*; D023041:Xenograft Model Antitumor Assays