Identifying the safety profile of a novel infectivity-enhanced conditionally replicative adenovirus, Ad5-Δ24-RGD, in anticipation of a phase I trial for recurrent ovarian cancer

OBJECTIVE: The purpose of this study was to evaluate the biodistribution and toxicity of the tropism-modified infectivity-enhanced conditionally replicative adenovirus, Ad5-Delta 24-arginine-glycine-aspartate (RGD). STUDY DESIGN: Cohorts of cotton rats were treated intravenously or intraperitoneally for 3 consecutive days with 5 x 10(8) to 5 x 10(11) particles/kg of Ad5-Delta 24-RGD or controls and killed on day 8, 17, or 56. For biodistribution studies, tissue samples from 14 organ sites and serum samples were evaluated for the presence of virus with the use of quantitative polymerase chain reaction analysis. For toxicity experiments, tissue samples from more than 30 organ sites and serum samples were obtained for the assessment of vector-related tissue or laboratory effects. RESULTS: Ad5-Delta 24-RGD was noted in tested samples at days 8 and 17 in animals that were treated intravenously and intraperitoneally with clearance by day 56. There were lower copies of vector noted in the blood and liver specimens of intraperitoneally treated animals. Mild peritonitis histopathologic findings were noted in rats that were treated intraperitoneally with Ad5-Delta 24-RGD; pathologic findings did not vary significantly with dose, over time, or in comparison to that noted in animals that were treated with Ad5-Delta 24. CONCLUSION: These studies provide critical insights regarding Ad5-Delta 24-RGD dosing and anticipated toxicity for a planned clinical trial for ovarian cancer.