title: Efficient colonization and therapy of human hepatocellular carcinoma (HCC) using the oncolytic vaccinia virus strain GLV-1h68.
abstract: Virotherapy using oncolytic vaccinia virus strains is one of the most promising new strategies for cancer therapy. In this study, we analyzed for the first time the therapeutic efficacy of the oncolytic vaccinia virus GLV-1h68 in two human hepatocellular carcinoma cell lines HuH7 and PLC/PRF/5 (PLC) in cell culture and in tumor xenograft models. By viral proliferation assays and cell survival tests, we demonstrated that GLV-1h68 efficiently colonized, replicated in, and did lyse these cancer cells in culture. Experiments with HuH7 and PLC xenografts have revealed that a single intravenous injection (i.v.) of mice with GLV-1h68 resulted in a significant reduction of primary tumor sizes compared to uninjected controls. In addition, replication of GLV-1h68 in tumor cells led to strong inflammatory and oncolytic effects resulting in intense infiltration of MHC class II-positive cells like neutrophils, macrophages, B cells and dendritic cells and in up-regulation of 13 pro-inflammatory cytokines. Furthermore, GLV-1h68 infection of PLC tumors inhibited the formation of hemorrhagic structures which occur naturally in PLC tumors. Interestingly, we found a strongly reduced vascular density in infected PLC tumors only, but not in the non-hemorrhagic HuH7 tumor model. These data demonstrate that the GLV-1h68 vaccinia virus may have an enormous potential for treatment of human hepatocellular carcinoma in man.
authors.affiliation: Genelux Corporation, San Diego Science Center, San Diego, California, United States of America.
authors.forename: Ivaylo
authors.initials: I
authors.lastname: Gentschev
authors.forename: Meike
authors.initials: M
authors.lastname: Müller
authors.forename: Marion
authors.initials: M
authors.lastname: Adelfinger
authors.forename: Stephanie
authors.initials: S
authors.lastname: Weibel
authors.forename: Friedrich
authors.initials: F
authors.lastname: Grummt
authors.forename: Martina
authors.initials: M
authors.lastname: Zimmermann
authors.forename: Michael
authors.initials: M
authors.lastname: Bitzer
authors.forename: Martin
authors.initials: M
authors.lastname: Heisig
authors.forename: Qian
authors.initials: Q
authors.lastname: Zhang
authors.forename: Yong A
authors.initials: YA
authors.lastname: Yu
authors.forename: Nanhai G
authors.initials: NG
authors.lastname: Chen
authors.forename: Jochen
authors.initials: J
authors.lastname: Stritzker
authors.forename: Ulrich M
authors.initials: UM
authors.lastname: Lauer
authors.forename: Aladar A
authors.initials: AA
authors.lastname: Szalay
mesh_terms: D000818:Animals; D006528:Carcinoma, Hepatocellular / Q000628:therapy*; D002460:Cell Line; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000235:genetics / Q000502:physiology; D002522:Chlorocebus aethiops; D005434:Flow Cytometry; D006801:Humans; D008113:Liver Neoplasms / Q000628:therapy; D051379:Mice; D008819:Mice, Nude; D050130:Oncolytic Virotherapy / Q000379:methods*; D050504:Oncolytic Viruses / Q000235:genetics / Q000502:physiology*; D014616:Vaccinia virus / Q000235:genetics / Q000502:physiology*; D014779:Virus Replication