Viruses | |
Preclinical Testing Oncolytic Vaccinia Virus Strain GLV-5b451 Expressing an Anti-VEGF Single-Chain Antibody for Canine Cancer Therapy | |
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
© 2015 by the authors; licensee MDPI, Basel, Switzerland.
【 预 览 】
Files | Size | Format | View |
---|---|---|---|
RO202003190009494ZK.pdf | 2646KB | download |