S.N. Jeong, S. Y.Yoo
Pusan National University,
Keywords: oncolytic virus, cancer suicide gene, normal vascular gene, virotherapy
Summary:We developed a new oncolytic vaccinia virus (NOV) with the dual advantages of cancer selectivity and normal vessel construction by adopting TRAIL and Angiopoietin. To demonstrate the cancer-specific and oncolytic potency of NOV, different panels of cancer cell lines (CRC, HCC, CC, PanC etc.) were tested. NOV were injected into tumor mice models and tumor growth and gene expressions was examined after treatment. Also, the early apoptotic cell population, which represents apoptosis, and its relation to oncolytic, was examined. NOV showed higher toxicity than the WT virus with TK deficiency in all the examined various ranges of cancer cell line (hepatocellular carcinoma, human epithelial adenocarcinoma, human bone osteosarcoma epithelial cell lines, murine melanoma, pancreatic cancer cell, metastatic pancreatic cancer cell etc). NOV treated CT26 mouse colon cancer xenograft model showed attenuated tumor growth resulting from successful lysis of cancer cells by NOV. The percentage of early stage in apoptosis of NOV treated group was much higher than that of WT virus. In addition, normal vessel construction by NOV was along with its antitumor activity and immunity. From results, we concluded that the improved antitumor effects of our novel oncolytic virus (NOV) is contributed both by specific proliferation only in cancer cells inducing their apoptosis and by normal vessel construction.