Characterization of Morreton virus as an oncolytic virotherapy platform for liver cancers

Background Morreton virus (MORV) is an oncolytic Vesiculovirus, genetically distinct from vesicular stomatitis virus (VSV). Aim To report that MORV induced potent cytopathic effects (CPEs) in cholangiocarcinoma (CCA) and hepatocellular carcinoma (HCC) in vitro models. Approach and Results In preliminary safety analyses, high intranasal doses (up to 10(10) 50% tissue culture infectious dose [TCID50]) of MORV were not associated with significant adverse effects in immune competent, non-tumor-bearing mice. MORV was shown to be efficacious in a Hep3B hepatocellular cancer xenograft model but not in a CCA xenograft HuCCT1 model. In an immune competent, syngeneic murine CCA model, single intratumoral treatments with MORV (1 x 10(7) TCID50) triggered a robust antitumor immune response leading to substantial tumor regression and disease control at a dose 10-fold lower than VSV (1 x 10(8) TCID50). MORV led to increased CD8(+) cytotoxic T cells without compensatory increases in tumor-associated macrophages and granulocytic or monocytic myeloid-derived suppressor cells. Conclusions Our findings indicate that wild-type MORV is safe and can induce potent tumor regression via immune-mediated and immune-independent mechanisms in HCC and CCA animal models without dose limiting adverse events. These data warrant further development and clinical translation of MORV as an oncolytic virotherapy platform.