title: Hepatocarcinoma cells constitutively expressing adenoviral E1-genes provide a tumor model for intratumoral replication of E1-deficient adenoviruses.
abstract: The elimination of malignant tumors by intratumoral virus replication is a challenging therapeutic approach but is critically dependent on the speed and efficacy of intratumoral virus spread. The expression of oncolytic transgenes in the context of a replicating virus may help to enhance the therapeutic potency of this strategy. We have established a human hepatocarcinoma-derived cell line (Huh7-E1) which stably expresses adenoviral E1-genes. Tumors derived from these cells support replication of E1-deficient adenoviruses in SCID mice. This model can be used to evaluate E1-negative viruses encoding reporter genes or oncolytic transgenes in a replicating context. Most oncolytic viruses for human use could then be re-engineered as E1-postive viruses. Moreover, Huh7-E1 tumors release human alpha-1-antitrypsin (hAAT), which allows the monitoring of occult growing tumors (i.e. liver, peritoneum) by measuring serum hAAT levels.
authors.affiliation: Department of Molecular Cell Biology, Institute for Biology, Humboldt University Berlin at the Max-Delbrueck-Center for Molecular Medicine, Germany. gcichon@mdc-berlin.de
authors.forename: Guenter
authors.initials: G
authors.lastname: Cichon
authors.forename: Susanne
authors.initials: S
authors.lastname: Boeckh-Herwig
authors.forename: Sefer
authors.initials: S
authors.lastname: Elezkurtaj
authors.forename: Hartmut H
authors.initials: HH
authors.lastname: Schmidt
authors.forename: Christian
authors.initials: C
authors.lastname: Hofmann
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Arnold
mesh_terms: D000256:Adenoviridae / Q000235:genetics* / Q000502:physiology; D017498:Adenovirus E1 Proteins / Q000096:biosynthesis / Q000235:genetics*; D000818:Animals; D006528:Carcinoma, Hepatocellular / Q000235:genetics / Q000378:metabolism / Q000628:therapy / Q000821:virology*; D002455:Cell Division / Q000502:physiology; D005814:Genes, Viral; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics / Q000378:metabolism / Q000628:therapy / Q000821:virology*; D051379:Mice; D016513:Mice, SCID; D014407:Tumor Cells, Cultured; D014779:Virus Replication; D023041:Xenograft Model Antitumor Assays; D000515:alpha 1-Antitrypsin / Q000378:metabolism
chemical_list: D017498:Adenovirus E1 Proteins; D000515:alpha 1-Antitrypsin