title: Attenuated Semliki Forest virus for cancer treatment in dogs: safety assessment in two laboratory Beagles.
abstract: BACKGROUND
  Dogs suffer from spontaneous tumors which may be amenable to therapies developed for human cancer patients, and dogs may serve as large-animal cancer models. A non-pathogenic Semliki Forest virus vector VA7-EGFP previously showed promise in targeting human tumor xenografts in mice, but the oncolytic capacity of the virus in canine cancer cells and the safety of the virus in higher mammals such as dogs, are not known. We therefore assessed the oncolytic potency of VA7-EGFP against canine cancer cells by infectivity and viability assays in two dog solid tumor cell lines. Furthermore we performed a 3-week safety study in two adult Beagles which received a single intravenous injection of ~2 × 10(5) plaque forming units of parental A7(74) strain.
  
  
  RESULTS
  VA7-EGFP was able to replicate in and kill both canine cancer cell lines tested. No adverse events were observed in either of the two virus-injected adult Beagles and no infective virus could be recovered from any of the biological samples collected over the course of the study. Neutralizing antibodies to Semliki Forest virus became detectable in the dogs at 5 days post infection and remained elevated until study termination.
  
  
  CONCLUSIONS
  Based on these results, testing of the oncolytic potential of attenuated Semliki Forest virus in canine cancer patients appears feasible.
authors.affiliation: Department of Equine and Small Animal Medicine, Faculty of Veterinary Medicine, University of Helsinki, P.O. Box 57, 00014, Helsinki, Finland. karoliina.autio@helsinki.fi.|Cancer Gene Therapy Group, Department of Pathology and Transplantation Laboratory, Haartman Institute, University of Helsinki, P.O. Box 21, 00014, Helsinki, Finland. karoliina.autio@helsinki.fi.
authors.forename: Karoliina P M
authors.initials: KP
authors.lastname: Autio
authors.affiliation: A. I. Virtanen Institute for Molecular Sciences, Biotechnology and Molecular Medicine, University of Eastern Finland, P.O. Box 1627, 70211, Kuopio, Finland. janne.j.ruotsalainen@uef.fi.
authors.forename: Janne J
authors.initials: JJ
authors.lastname: Ruotsalainen
authors.affiliation: Finnish Food Safety Authority Evira, Pathology Unit, Mustialankatu 3, 00790, Helsinki, Finland. marjukka.anttila@evira.fi.
authors.forename: Marjukka O
authors.initials: MO
authors.lastname: Anttila
authors.affiliation: A. I. Virtanen Institute for Molecular Sciences, Biotechnology and Molecular Medicine, University of Eastern Finland, P.O. Box 1627, 70211, Kuopio, Finland. minna.niittykoski@uef.fi.
authors.forename: Minna
authors.initials: M
authors.lastname: Niittykoski
authors.affiliation: Department of Virology, University of Turku, 20014, Turku, Finland. mwaris@utu.fi.
authors.forename: Matti
authors.initials: M
authors.lastname: Waris
authors.affiliation: Cancer Gene Therapy Group, Department of Pathology and Transplantation Laboratory, Haartman Institute, University of Helsinki, P.O. Box 21, 00014, Helsinki, Finland. akseli.hemminki@helsinki.fi.
authors.forename: Akseli
authors.initials: A
authors.lastname: Hemminki
authors.affiliation: Institute of Biotechnology, University of Helsinki, P.O. Box 56, 00014, Helsinki, Finland. markus.vaha-koskela@helsinki.fi.
authors.forename: Markus J V
authors.initials: MJ
authors.lastname: Vähä-Koskela
authors.affiliation: A. I. Virtanen Institute for Molecular Sciences, Biotechnology and Molecular Medicine, University of Eastern Finland, P.O. Box 1627, 70211, Kuopio, Finland. ari.hinkkanen@uef.fi.
authors.forename: Ari E
authors.initials: AE
authors.lastname: Hinkkanen
mesh_terms: D000818:Animals; D057134:Antibodies, Neutralizing / Q000097:blood; D019496:Cancer Vaccines / Q000009:adverse effects*; D045744:Cell Line, Tumor; D004283:Dog Diseases / Q000139:chemically induced*; D004285:Dogs; D005260:Female; D012672:Semliki forest virus; D014779:Virus Replication / Q000502:physiology
chemical_list: D057134:Antibodies, Neutralizing; D019496:Cancer Vaccines