Evolutionary cancer-favoring engineered vaccinia virus for metastatic hepatocellular carcinoma

Abstract

Engineered vaccinia virus-based therapy shows promising results in patients with advanced hepatocellular carcinoma, although a strategic virus design for the metastatic liver and the study of its efficacy in treating the cancer has not been well assessed. In this paper, we proposed a simple and strategic virus design for targeting metastatic hepatocellular carcinoma. We developed an evolutionary cancer-favoring engineered vaccinia virus (CVV, which is produced by repeated selective replication in cancerous tissues and then deleting viral thymidine kinase genes) and investigated its therapeutic effects on metastatic liver cancer. The expression of the cell surface marker, CD44, which is associated with cancer stem cells, seems to be correlated with the cells’ metastatic characteristics; cellular migration, epithelial-mesenchymal transition (EMT) expression and liver tumorigenicity. The highly metastatic and tumorigenic Sk-Hep-1 cell line was selected and injected directly onto the liver tissue to develop a liver-to-colon metastasis model. In an animal study, the subjects were treated with sorafenib, CVV, or sorafenib with CVV. Metastatic regions were interestingly rare in the CVV-treated groups (i.e., CVV or sorafenib with CVV) whereas metastatic regions existed in the sorafenib-treated group. From results, we concluded that our simple strategy of developing a cancer-favoring virus can successfully eradicate metastatic liver cancer cells, provided that our CVV can be a promising therapeutic virus that targets metastatic liver cancer.