title: Preclinical Testing Oncolytic Vaccinia Virus Strain GLV-5b451 Expressing an Anti-VEGF Single-Chain Antibody for Canine Cancer Therapy.
abstract: Virotherapy on the basis of oncolytic vaccinia virus (VACV) strains is a novel approach for canine cancer therapy. Here we describe, for the first time, the characterization and the use of VACV strain GLV-5b451 expressing the anti-vascular endothelial growth factor (VEGF) single-chain antibody (scAb) GLAF-2 as therapeutic agent against different canine cancers. Cell culture data demonstrated that GLV-5b451 efficiently infected and destroyed all four tested canine cancer cell lines including: mammary carcinoma (MTH52c), mammary adenoma (ZMTH3), prostate carcinoma (CT1258), and soft tissue sarcoma (STSA-1). The GLV-5b451 virus-mediated production of GLAF-2 antibody was observed in all four cancer cell lines. In addition, this antibody specifically recognized canine VEGF. Finally, in canine soft tissue sarcoma (CSTS) xenografted mice, a single systemic administration of GLV-5b451 was found to be safe and led to anti-tumor effects resulting in the significant reduction and substantial long-term inhibition of tumor growth. A CD31-based immuno-staining showed significantly decreased neo-angiogenesis in GLV-5b451-treated tumors compared to the controls. In summary, these findings indicate that GLV-5b451 has potential for use as a therapeutic agent in the treatment of CSTS.
authors.affiliation: Department of Biochemistry, Theodor-Boveri-Institute, University of Wuerzburg, D-97074 Wuerzburg, Germany. marion.adelfinger@biozentrum.uni-wuerzburg.de.
authors.forename: Marion
authors.initials: M
authors.lastname: Adelfinger
authors.affiliation: Department of Biochemistry, Theodor-Boveri-Institute, University of Wuerzburg, D-97074 Wuerzburg, Germany. simon.bessler@stud-mail.uni-wuerzburg.de.
authors.forename: Simon
authors.initials: S
authors.lastname: Bessler
authors.affiliation: Genelux Corporation, San Diego Science Center, San Diego, CA 92109, USA. afrentzen@genelux.com.
authors.forename: Alexa
authors.initials: A
authors.lastname: Frentzen
authors.affiliation: Department of Biochemistry, Theodor-Boveri-Institute, University of Wuerzburg, D-97074 Wuerzburg, Germany. alexander.cecil@biozentrum.uni-wuerzburg.de.|Department of Bioinformatics, Theodor-Boveri-Institute, University of Wuerzburg, Biocenter, D-97074 Wuerzburg, Germany. alexander.cecil@biozentrum.uni-wuerzburg.de.
authors.forename: Alexander
authors.initials: A
authors.lastname: Cecil
authors.affiliation: Department of Biochemistry, Theodor-Boveri-Institute, University of Wuerzburg, D-97074 Wuerzburg, Germany. johanna.langbein@biozentrum.uni-wuerzburg.de.
authors.forename: Johanna
authors.initials: J
authors.lastname: Langbein-Laugwitz
authors.affiliation: Department of Biochemistry, Theodor-Boveri-Institute, University of Wuerzburg, D-97074 Wuerzburg, Germany. ivaylo.gentschev@mail.uni-wuerzburg.de.|Genelux Corporation, San Diego Science Center, San Diego, CA 92109, USA. ivaylo.gentschev@mail.uni-wuerzburg.de.
authors.forename: Ivaylo
authors.initials: I
authors.lastname: Gentschev
authors.affiliation: Department of Biochemistry, Theodor-Boveri-Institute, University of Wuerzburg, D-97074 Wuerzburg, Germany. szalay@biozentrum.uni-wuerzburg.de.|Genelux Corporation, San Diego Science Center, San Diego, CA 92109, USA. szalay@biozentrum.uni-wuerzburg.de.|Department of Radiation Oncology, Rebecca & John Moores Comprehensive Cancer Center, University of California, San Diego, La Jolla, CA 92093, USA. szalay@biozentrum.uni-wuerzburg.de.
authors.forename: Aladar A
authors.initials: AA
authors.lastname: Szalay
mesh_terms: D000818:Animals; D004283:Dog Diseases / Q000235:genetics / Q000378:metabolism / Q000628:therapy*; D004285:Dogs; D005260:Female; D051379:Mice; D008819:Mice, Nude; D009369:Neoplasms / Q000235:genetics / Q000276:immunology / Q000628:therapy / Q000662:veterinary*; D050130:Oncolytic Virotherapy; D050504:Oncolytic Viruses / Q000235:genetics* / Q000378:metabolism; D057127:Single-Chain Antibodies / Q000235:genetics / Q000276:immunology* / Q000627:therapeutic use; D014616:Vaccinia virus / Q000235:genetics* / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000276:immunology*
chemical_list: D057127:Single-Chain Antibodies; D042461:Vascular Endothelial Growth Factor A
keywords: angiogenesis; antibody production; cancer; canine cancer cell lines; canine cancer therapy; canine soft tissue sarcoma (CSTS); oncolytic virus