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Viruses 2015, 7(7), 4075-4092; doi:10.3390/v7072811

Preclinical Testing Oncolytic Vaccinia Virus Strain GLV-5b451 Expressing an Anti-VEGF Single-Chain Antibody for Canine Cancer Therapy

1
Department of Biochemistry, Theodor-Boveri-Institute, University of Wuerzburg, D-97074 Wuerzburg, Germany
2
Genelux Corporation, San Diego Science Center, San Diego, CA 92109, USA
3
Department of Bioinformatics, Theodor-Boveri-Institute, University of Wuerzburg, Biocenter, D-97074 Wuerzburg, Germany
4
Department of Radiation Oncology, Rebecca & John Moores Comprehensive Cancer Center, University of California, San Diego, La Jolla, CA 92093, USA
*
Authors to whom correspondence should be addressed.
Academic Editors: E. Antonio Chiocca and Martine L.M. Lamfers
Received: 27 April 2015 / Revised: 8 July 2015 / Accepted: 16 July 2015 / Published: 20 July 2015
(This article belongs to the Special Issue Oncolytic Viruses)
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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. View Full-Text
Keywords: oncolytic virus; cancer; canine cancer cell lines; antibody production; angiogenesis; canine soft tissue sarcoma (CSTS); canine cancer therapy oncolytic virus; cancer; canine cancer cell lines; antibody production; angiogenesis; canine soft tissue sarcoma (CSTS); canine cancer therapy
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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MDPI and ACS Style

Adelfinger, M.; Bessler, S.; Frentzen, A.; Cecil, A.; Langbein-Laugwitz, J.; Gentschev, I.; Szalay, A.A. Preclinical Testing Oncolytic Vaccinia Virus Strain GLV-5b451 Expressing an Anti-VEGF Single-Chain Antibody for Canine Cancer Therapy. Viruses 2015, 7, 4075-4092.

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