Differential biodistribution of oncolytic poxvirus administered systemically in an autochthonous model of hepatocellular carcinoma.
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.
INSERM U948, Nantes, France; Centre de Biophysique Moléculaire, CNRS, UPR4301, Univerity of Orléans, France.
Patrick
P
Baril
Yann
Y
Touchefeu
Jeannette
J
Cany
Yan
Y
Cherel
Steve H
SH
Thorne
Lucile
L
Tran
Sophie
S
Conchon
Georges
G
Vassaux
D000818:Animals; D019496:Cancer Vaccines / Q000008:administration & dosage / Q000235:genetics; D006528:Carcinoma, Hepatocellular / Q000235:genetics / Q000628:therapy / Q000821:virology; D045744:Cell Line, Tumor; D005822:Genetic Vectors; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics / Q000628:therapy / Q000821:virology; D051379:Mice; D009374:Neoplasms, Experimental / Q000235:genetics / Q000628:therapy / Q000821:virology; D050130:Oncolytic Virotherapy; D050504:Oncolytic Viruses / Q000235:genetics*; D011212:Poxviridae / Q000235:genetics*; D014018:Tissue Distribution
D019496:Cancer Vaccines