Cationic Lipid DNA Complex (JVRS-100) treatment of woodchucks with Hepatitis B virus induced Hepatocellular Carcinoma (154.12)

Abstract

Abstract To determine the dependence of responsiveness to immune stimulation on the woodchuck hepatitis B viral (wHBV) load, we evaluated cytokine and cell surface marker mRNA expression following dosing of JVRS-100 in chronic woodchuck carriers with low (mean: 2.2x1010 ge/ml), medium (4.0x1010 ge/ml) and high (4.2x1011 ge/ml) serum viral loads. Our hypothesis was that high viral loads seen in chronic wHBV infection (10x human) result in immune suppression to external immune stimuli. Woodchucks were dosed intravenously with JVRS-100 and evaluated for immune activation. Woodchucks with low viral load had increased expression of cytokine and cell surface markers in contrast to animals with moderate or high viral loads with no change in expression. To evaluate anti-tumor effects of JVRS-100 we dosed groups of woodchucks with 100µg or 300µg JVRS-100. When normalized for pre-treatment levels of wHBV serum DNA, there was a steady decrease in viral load of treated woodchucks. There was no difference in the tumor burden; however, woodchucks in the high dose JVRS-100 group developed no new tumors over the 24 weeks in which they were monitored (12 weeks Rx followed by 12 weeks observation). This is unusual for this disease model and we believe highly significant to the development of an intervention for HBV induced HCC. Our working hypothesis is that the administration of JVRS-100 blocks the conversion of chronic HBV infection to HCC.