Evolutionary cancer-favoring engineered vaccinia virus for metastatic hepatocellular carcinoma

// So Young Yoo 1, 2, 3 , Su-Nam Jeong 1 , Dae Hwan Kang 2, 3 and Jeong Heo 3 1 BIO-IT Foundry Technology Institute, Pusan National University, Busan 609-735, Republic of Korea 2 Research Institute for Convergence of Biomedical Science and Technology, Pusan National University Yangsan Hospital, Yangsan 626-770, Republic of Korea 3 Department of Internal Medicine, College of Medicine, Pusan National University and Medical Research Institute, Busan 602-739, Republic of Korea Correspondence to: So Young Yoo, email: yoosy2@gmail.com , yoosy@pusan.ac.kr Jeong Heo, email: sodium@korea.com Keywords: hepatocellular carcinoma (HCC), oncolytic virus, cancer-favoring vaccinia virus, Wyeth strain, metastasis Received: December 08, 2016 Accepted: April 11, 2017 Published: April 20, 2017 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.