Differential biodistribution of oncolytic poxvirus administered systemically in an autochthonous model of hepatocellular carcinoma.

Abstract : BACKGROUND: Pre-clinical studies have demonstrated that unlike oncolytic adenoviruses, oncolytic vaccinia viruses can reach implanted tumors upon systemic injection. However, the biodistribution of this oncolytic agent in in-situ, autochthonous tumor models remains poorly characterized. In the present study, we have assessed this biodistribution in a model of mouse hepatocellular carcinoma (HCC) obtained after injection of the carcinogen diethylnitrosamine (DEN). METHODS: Twelve months after DEN administration, histology, quantitative RT-PCR, in situ hybridization as well as viral titration were used to characterize tumors and to assess the viral load of the livers upon either intravenous or intraperitoineal injection. RESULTS: The results showed that the architecture of the liver was lost, with a noticeable absence of sinusoids as well as presence of steatosis and the presence of α-fetoprotein-positive, HCC tumor nodules. Bioluminescence imaging as well as measures of the infective virus load demonstrated that intravenous injection of 10(8) pfu of the recombinant vaccinia virus led to a predominant transduction of the liver, while intraperitoneal injection resulted in a lower level of liver transduction accompanied by an increased infection of the lungs, spleen, kidneys and bowels. Immunohistochemical analysis of liver sections of animals injected intravenously with the virus revealed a preferential localization of vaccinia-specific immuno-reactivity in the tumors. CONCLUSION: This study emphasizes the importance of the route of administration of the vector and highlights the relevance of systemic injection of oncolytic vaccinia virus in the context of hepatocellular carcinoma. Copyright © 2011 John Wiley & Sons, Ltd.
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Patrick Baril, Yann Touchefeu, Jeannette Cany, Yan Cherel, Steve H Thorne, et al.. Differential biodistribution of oncolytic poxvirus administered systemically in an autochthonous model of hepatocellular carcinoma.. The Journal of Gene Medicine, Wiley, 2011, 13 (12), pp.692-701. ⟨10.1002/jgm.1624⟩. ⟨hal-00720514⟩

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