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.
Highlights
Cancer is the major cause of canine death in both developed and developing countries [1]
vascular endothelial growth factor (VEGF) is a potent mediator of both angiogenesis and vasculogenesis in dogs and has been proposed as a prognostic indicator in several several types types of of canine canine cancer cancer [10,13,26]
The results revealed that CT1258 cells produced about 25-fold more
Summary
Cancer is the major cause of canine death in both developed and developing countries [1]. The major treatment options for canine cancers include surgery, radiation therapy, chemotherapy, hyperthermia and photodynamic therapy. One of the most promising novel cancer therapies is oncolytic virotherapy. This method is based on the capacity of oncolytic viruses (OVs) to preferentially infect and lyse cancer cells without causing excessive damage to surrounding normal tissue. Several oncolytic viruses including various human and canine adenoviruses, canine distemper virus and vaccinia virus strains have been successfully tested for canine cancer therapy in preclinical settings In contrast to human studies, the clinical trials with oncolytic viruses for canine cancer patients are just at the beginning
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