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

Viruses

Marion Adelfinger¹  Simon Bessler¹  Alexa Frentzen³  Alexander Cecil¹  Johanna Langbein-Laugwitz¹  Ivaylo Gentschev¹  Aladar A. Szalay¹  E. Antonio Chiocca² 

[1] Department of Biochemistry, Theodor-Boveri-Institute, University of Wuerzburg, D-97074 Wuerzburg, Germany; E-Mails:Department of Biochemistry, Theodor-Boveri-Institute, University of Wuerzburg, D-97074 Wuerzburg, Germany;;Genelux Corporation, San Diego Science Center, San Diego, CA 92109, USA; E-Mail:

关键词: oncolytic virus;    cancer;    canine cancer cell lines;    antibody production;    angiogenesis;    canine soft tissue sarcoma (CSTS);    canine cancer therapy;   

DOI  :  10.3390/v7072811

来源: mdpi

【 摘 要 】

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.

【 授权许可】

CC BY   
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