Abstract
Virotherapy using oncolytic vaccinia virus (VACV) strains is one promising new strategy for canine cancer therapy. In this study we describe the establishment of an in vivo model of canine soft tissue sarcoma (CSTS) using the new isolated cell line STSA-1 and the analysis of the virus-mediated oncolytic and immunological effects of two different Lister VACV LIVP1.1.1 and GLV-1h68 strains against CSTS. Cell culture data demonstrated that both tested VACV strains efficiently infected and destroyed cells of the canine soft tissue sarcoma line STSA-1. In addition, in our new canine sarcoma tumor xenograft mouse model, systemic administration of LIVP1.1.1 or GLV-1h68 viruses led to significant inhibition of tumor growth compared to control mice. Furthermore, LIVP1.1.1 mediated therapy resulted in almost complete tumor regression and resulted in long-term survival of sarcoma-bearing mice. The replication of the tested VACV strains in tumor tissues led to strong oncolytic effects accompanied by an intense intratumoral infiltration of host immune cells, mainly neutrophils. These findings suggest that the direct viral oncolysis of tumor cells and the virus-dependent activation of tumor-associated host immune cells could be crucial parts of anti-tumor mechanism in STSA-1 xenografts. In summary, the data showed that both tested vaccinia virus strains and especially LIVP1.1.1 have great potential for effective treatment of CSTS.
Highlights
Canine soft tissue sarcomas (CSTSs) typically arise in middleage to old dogs and are a diverse group of cancers that collectively comprise 7% of cutaneous and 15% of subcutaneous canine cancers [1,2,3,4,5]
Alkaline phosphatase (ALP) activity is detectable in cells derived from bone, liver, kidney and intestine; CD18 is a marker for histiocytic cells; cytokeratin is found within cells of epithelial origin; and vimentin is present in mesenchymal cells
We investigated the oncolytic efficiency of two vaccinia virus strains GLV-1h68 and LIVP1.1.1, against a new canine soft tissue sarcoma cell line in culture and in a xenograft model
Summary
Canine soft tissue sarcomas (CSTSs) typically arise in middleage to old dogs and are a diverse group of cancers that collectively comprise 7% of cutaneous and 15% of subcutaneous canine cancers [1,2,3,4,5]. CSTSs have similarity in histological features and clinical behavior, these tumors are phenotypically diverse with frequently controversial histogenesis [6]. They include fibrosarcomas, myxosarcomas, liposarcomas, perivascular wall tumors, peripheral nerve sheath tumors (PNST), pleomorphic sarcoma, mesenchymoma, leiomyosarcoma and rhabdomyosarcomas [1,2,6,7]. Grade III tumors are uncommon and are thought to have a higher rate of recurrence and metastasis [6]
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