Comparison between intratumoral and intravenously administered oncolytic virus therapy with Newcastle disease virus in a xenograft murine model for pancreatic adenocarcinoma

Abstract

Pancreatic ductal adenocarcinoma (PDAC) is characterized by a poor clinical prognosis and is usually a metastatic disease. In the last decades, oncolytic viro-immunotherapy has shown a promise as treatment strategy with encouraging results for a variety of tumors. Newcastle Disease Virus (NDV) is an oncolytic virus which selectively infects and damages tumors either by directly killing tumor cells or by promoting an anti-tumor immune response. Several studies have demonstrated that NDV strains with a multi-basic cleavage site (MBCS) in the fusion protein (F) have increased anti-tumor efficacy upon intratumoral injection in murine tumor models. However, intravenous injections, in which the oncolytic virus spreads systemically, could be more beneficial to treat metastasized PDAC in addition to the primary tumor. In this study, we compared the oncolytic efficacy and safety of intratumoral and intravenous injections with NDV containing an MBCS in F (NDV F3aa) in an immune deficient murine xenograft (BxPC3) model for PDAC. In this model, both intratumoral and intravenous injections with NDV F3aa induced anti-tumor efficacy as measured at 10 days after the first injection. Upon intravenous injection virus was detected in some of the tumors, indicating the systemic spread of the virus. Upon both treatments, mice did not display weight loss or abnormalities and treated mice did not secrete virus to the environment. These data demonstrate that intravenous injections of NDV F3aa can be applicable to treat metastasized cancers in immune deficient hosts without inflicting adverse effects.

Keywords

• Newcastle disease virus
• Oncolytic viruses
• Safety
• Treatment efficacy
• Intravenous administration
• Intratumoral administration