Premium
Differential biodistribution of oncolytic poxvirus administered systemically in an autochthonous model of hepatocellular carcinoma
Author(s) -
Baril Patrick,
Touchefeu Yann,
Cany Jeannette,
Cherel Yan,
Thorne Steve H.,
Tran Lucile,
Conchon Sophie,
Vassaux Georges
Publication year - 2011
Publication title -
the journal of gene medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.689
H-Index - 91
eISSN - 1521-2254
pISSN - 1099-498X
DOI - 10.1002/jgm.1624
Subject(s) - oncolytic virus , vaccinia , hepatocellular carcinoma , biodistribution , virus , systemic administration , virology , pathology , medicine , liver cancer , cancer research , biology , in vivo , recombinant dna , biochemistry , microbiology and biotechnology , gene
Background Preclinical 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 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 reverse transcription‐polymerase chain reaction, in situ hybridization and viral titration were used to characterize tumors, as well as to assess the viral load of the livers upon either intravenous or intraperitoineal injection. Results The results obtained showed that the architecture of the liver was lost, with a noticeable absence of sinusoids, as well as the presence of steatosis and α‐fetoprotein‐positive HCC tumor nodules. Bioluminescence imaging and measures of the infective virus load demonstrated that intravenous injection of 10 8 plaque‐forming units of the recombinant vaccinia virus led to a predominant transduction of the liver, whereas 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 immunoreactivity in the tumors. Conclusions The findings of the present study emphasize the importance of the route of administration of the vector and highlight the relevance of systemic injection of oncolytic vaccinia virus in the context of hepatocellular carcinoma. Copyright © 2011 John Wiley & Sons, Ltd.