Characterization of Morreton Virus (MORV) as a Novel Oncolytic Virotherapy Platform for Liver Cancers

Abstract

Morreton virus (MORV) is a novel oncolytic Vesiculovirus, genetically distinct from vesicular stomatitis virus (VSV). we report that MORV induced potent cytopathic effects in a panel of cholangiocarcinoma (CCA) and hepatocellular carcinoma (HCC) cell lines. In addition, high intranasal doses of MORV were not associated with significant adverse effects and were well tolerated in mice bearing liver tumor xenografts and syngeneic liver cancers. Furthermore, single intratumoral treatments with MORV (1 x 107 TCID50) triggered a robust antitumor immune response leading to substantial tumor regression and disease control in a syngeneic CCA model, using 10-fold lower dose compared to VSV (1 x 108 TCID50). In addition, MORV and VSV both induced prominent tumor growth delay in immunodeficient mice bearing Hep3B hepatocellular carcinoma (HCC) but not in mice bearing HuCCT-1 CCA xenografts. Our findings indicate that wild-type MORV is safe and can induce potent tumor regression in HCC and CCA animal models without adverse events via immune-mediated and immune-independent mechanisms. Further development and clinical translation of MORV as virotherapy for liver cancers are warranted.

In vivo Safety and Immunoactivity of Oncolytic Jurona Virus in Hepatocellular Carcinoma: A Comprehensive Proteogenomic Analysis

“…We have previously shown that responsiveness to I IFN production or viral kinetic in vitro by infected cancer cell lines does not always correlate with in vivo efficacy to oncolytic. 4 To determine whether JURV can induce an oncolysis-dependent tumor growth delay, we injected IT three doses of JURV into the immunocompromised HEP3B-xenografts. We employed luciferase tagged HEP3B cells to monitor tumor growth during the first three weeks of treatment.…”

“…Rhabdoviruses possess several advantageous properties over other oncolytic viral vector platforms, including amenability to genetic manipulation, and not using humans as a natural host resulting in low seroprevalence in the population. 5 In addition to an episomal 85 and fast kinetic cycle in tumor cells, most vesiculoviruses can encode large transgenes 4 while maintaining the ability to potently infect, replicate and induce apoptosis 86,87 in a vast array of cancer cells. [88][89][90][91][92][93][94] We and others have shown that others non-vesicular stomatitis virus (VSV) members 4,95 of the Rhabdoviridae family have tremendous potential as oncolytic agents because of their natural tumor selectivity and hypersensitivity to type 1 interferon response which is defective in 80% of tumors.…”

“…5 In addition to an episomal 85 and fast kinetic cycle in tumor cells, most vesiculoviruses can encode large transgenes 4 while maintaining the ability to potently infect, replicate and induce apoptosis 86,87 in a vast array of cancer cells. [88][89][90][91][92][93][94] We and others have shown that others non-vesicular stomatitis virus (VSV) members 4,95 of the Rhabdoviridae family have tremendous potential as oncolytic agents because of their natural tumor selectivity and hypersensitivity to type 1 interferon response which is defective in 80% of tumors. 6,7 We described the anti-cancer potential of a laboratory attenuated Jurona virus…”

“…We have previously shown that responsiveness to I IFN production or viral kinetic in vitro by infected cancer cell lines does not always correlate with in vivo efficacy to oncolytic. 4 To determine whether JURV can induce an oncolysis-dependent tumor down-regulated proteins (Fig. 7 e, f).…”

“…In this study, we reported that Jurona virus (JURV) 4, 5 a non-VSV vesiculovirus JURV can effectively induce oncolysis in vitro, in animal models of HCC and prime systemic anti-tumor immunity resulting in robust tumor regression in syngeneic and xenograft hepatocellular carcinoma (HCC) models. Co-administration of JURV with immune checkpoint blockade antibodies profoundly modulated the tumor microenvironment via increase infiltration of cytotoxic T cells.…”