Oncolytic Properties of the Chimeric Poxvirus HOV-2 in Cholangiocarcinoma Models

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BACKGROUND: Cholangiocarcinoma (CCA) is a neoplasm of the biliary system and the second-most common primary hepatic malignancy. Neoadjuvant chemotherapy has become mainstay; however, 5-year survival rates remain poor, prompting the need for more treatment options. Oncolytic viruses selectively replicate in cancer cells and lyse them, representing a novel class of cancer therapeutics. We have developed a chimeric poxvirus that has enhanced oncolytic properties compared with other poxvirus strains. In this study, we evaluated the oncolytic properties of this chimeric poxvirus (HOV-2) in CCA models. STUDY DESIGN: Standard plaque assays and cytotoxicity assays were performed to evaluate the ability of the oncolytic virus to replicate in and kill CCA cells, respectively. The KMBC human CCA cell line was used to generate a xenograft model in athymic nude mice. Bilateral subcutaneous tumors were generated by injecting the cells into the lower flank areas, then the mice were administered a single dose of virus either through the intratumoral or intravenous route. RESULTS: HOV-2 effectively replicates in and kills multiple subtypes of CCA cells in a time and dose-dependent manner in vitro. In the KMBC xenograft model, both intratumoral and intravenous HOV-2 treatments were found to be efficient, resulting in near complete tumor control. All animals tolerated the treatments well. CONCLUSIONS: In a human xenograft CCA tumor model, HOV-2 causes significant tumor regression with minimal toxicity. These results signify HOV-2 as a safe and effective treatment in a preclinical model of CCA.

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