title: Virotherapy of canine tumors with oncolytic vaccinia virus GLV-1h109 expressing an anti-VEGF single-chain antibody.
abstract: Virotherapy using oncolytic vaccinia virus (VACV) strains is one promising new strategy for cancer therapy. We have previously reported that oncolytic vaccinia virus strains expressing an anti-VEGF (Vascular Endothelial Growth Factor) single-chain antibody (scAb) GLAF-1 exhibited significant therapeutic efficacy for treatment of human tumor xenografts. Here, we describe the use of oncolytic vaccinia virus GLV-1h109 encoding GLAF-1 for canine cancer therapy. In this study we analyzed the virus-mediated delivery and production of scAb GLAF-1 and the oncolytic and immunological effects of the GLV-1h109 vaccinia virus strain against canine soft tissue sarcoma and canine prostate carcinoma in xenograft models. Cell culture data demonstrated that the GLV-1h109 virus efficiently infect, replicate in and destroy both tested canine cancer cell lines. In addition, successful expression of GLAF-1 was demonstrated in virus-infected canine cancer cells and the antibody specifically recognized canine VEGF. In two different xenograft models, the systemic administration of the GLV-1h109 virus was found to be safe and led to anti-tumor and immunological effects resulting in the significant reduction of tumor growth in comparison to untreated control mice. Furthermore, tumor-specific virus infection led to a continued production of functional scAb GLAF-1, resulting in inhibition of angiogenesis. Overall, the GLV-1h109-mediated cancer therapy and production of immunotherapeutic anti-VEGF scAb may open the way for combination therapy concept i.e. vaccinia virus mediated oncolysis and intratumoral production of therapeutic drugs in canine cancer patients.
authors.affiliation: Department of Biochemistry, University of Wuerzburg, Wuerzburg, Germany.
authors.forename: Sandeep S
authors.initials: SS
authors.lastname: Patil
authors.forename: Ivaylo
authors.initials: I
authors.lastname: Gentschev
authors.forename: Marion
authors.initials: M
authors.lastname: Adelfinger
authors.forename: Ulrike
authors.initials: U
authors.lastname: Donat
authors.forename: Michael
authors.initials: M
authors.lastname: Hess
authors.forename: Stephanie
authors.initials: S
authors.lastname: Weibel
authors.forename: Ingo
authors.initials: I
authors.lastname: Nolte
authors.forename: Alexa
authors.initials: A
authors.lastname: Frentzen
authors.forename: Aladar A
authors.initials: AA
authors.lastname: Szalay
mesh_terms: D000818:Animals; D002460:Cell Line; D002470:Cell Survival; D004283:Dog Diseases / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D004285:Dogs; D005260:Female; D015870:Gene Expression; D023061:Gene Order; D005822:Genetic Vectors / Q000008:administration & dosage / Q000235:genetics* / Q000493:pharmacokinetics; D005966:Glucuronidase / Q000235:genetics / Q000378:metabolism; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D009369:Neoplasms / Q000276:immunology / Q000628:therapy / Q000662:veterinary*; D050130:Oncolytic Virotherapy; D057127:Single-Chain Antibodies / Q000235:genetics* / Q000378:metabolism; D047368:Tumor Burden; D014616:Vaccinia virus / Q000235:genetics*; D042461:Vascular Endothelial Growth Factor A / Q000037:antagonists & inhibitors* / Q000276:immunology; D014779:Virus Replication; D023041:Xenograft Model Antitumor Assays
chemical_list: D057127:Single-Chain Antibodies; D042461:Vascular Endothelial Growth Factor A; D005966:Glucuronidase