Virotherapy using oncolytic vaccinia virus strains is one of the most promising new strategies for
cancer therapy. In this study, we analyzed for the first time the therapeutic efficacy of the oncolytic vaccinia virus GLV-1h68 in two human
hepatocellular carcinoma cell lines HuH7 and PLC/PRF/5 (PLC) in cell culture and in
tumor xenograft models. By viral proliferation assays and cell survival tests, we demonstrated that GLV-1h68 efficiently colonized, replicated in, and did lyse these
cancer cells in culture. Experiments with HuH7 and PLC xenografts have revealed that a single
intravenous injection (i.v.) of mice with GLV-1h68 resulted in a significant reduction of primary
tumor sizes compared to uninjected controls. In addition, replication of GLV-1h68 in
tumor cells led to strong inflammatory and oncolytic effects resulting in intense infiltration of MHC class II-positive cells like neutrophils, macrophages, B cells and dendritic cells and in up-regulation of 13 pro-inflammatory
cytokines. Furthermore, GLV-1h68
infection of PLC
tumors inhibited the formation of hemorrhagic structures which occur naturally in PLC
tumors. Interestingly, we found a strongly reduced vascular density in infected PLC
tumors only, but not in the non-hemorrhagic HuH7
tumor model. These data demonstrate that the GLV-1h68 vaccinia virus may have an enormous potential for treatment of human
hepatocellular carcinoma in man.