title: Identifying the safety profile of a novel infectivity-enhanced conditionally replicative adenovirus, Ad5-delta24-RGD, in anticipation of a phase I trial for recurrent ovarian cancer.
abstract: OBJECTIVE
  The purpose of this study was to evaluate the biodistribution and toxicity of the tropism-modified infectivity-enhanced conditionally replicative adenovirus, Ad5-delta24-arginine-glycine-aspartate (RGD).
  
  
  METHODS
  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-delta24-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-delta24-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-delta24-RGD; pathologic findings did not vary significantly with dose, over time, or in comparison to that noted in animals that were treated with Ad5-delta24.
  
  
  CONCLUSIONS
  These studies provide critical insights regarding Ad5-delta24-RGD dosing and anticipated toxicity for a planned clinical trial for ovarian cancer.
authors.affiliation: Southern Research Institute, Birmingham, AL, USA.
authors.forename: John G
authors.initials: JG
authors.lastname: Page
authors.forename: Baohong
authors.initials: B
authors.lastname: Tian
authors.forename: Karen
authors.initials: K
authors.lastname: Schweikart
authors.forename: Joseph
authors.initials: J
authors.lastname: Tomaszewski
authors.forename: Ray
authors.initials: R
authors.lastname: Harris
authors.forename: Trevor
authors.initials: T
authors.lastname: Broadt
authors.forename: Judith
authors.initials: J
authors.lastname: Polley-Nelson
authors.forename: Patricia E
authors.initials: PE
authors.lastname: Noker
authors.forename: Minghui
authors.initials: M
authors.lastname: Wang
authors.forename: Sharmila
authors.initials: S
authors.lastname: Makhija
authors.forename: Rose
authors.initials: R
authors.lastname: Aurigemma
authors.forename: David T
authors.initials: DT
authors.lastname: Curiel
authors.forename: Ronald D
authors.initials: RD
authors.lastname: Alvarez
mesh_terms: D000256:Adenoviridae; D000704:Analysis of Variance; D000818:Animals; D004195:Disease Models, Animal; D005260:Female; D018014:Gene Transfer Techniques; D005822:Genetic Vectors / Q000494:pharmacology; D007274:Injections, Intraperitoneal; D007275:Injections, Intravenous; D009364:Neoplasm Recurrence, Local / Q000175:diagnosis / Q000401:mortality / Q000628:therapy*; D009842:Oligopeptides / Q000494:pharmacology*; D050130:Oncolytic Virotherapy / Q000379:methods*; D010051:Ovarian Neoplasms / Q000401:mortality / Q000628:therapy*; D016133:Polymerase Chain Reaction; D011336:Probability; D011897:Random Allocation; D051381:Rats; D011919:Rats, Inbred Strains; D012016:Reference Values; D012680:Sensitivity and Specificity; D016205:Sigmodontinae; D016019:Survival Analysis
chemical_list: D009842:Oligopeptides; C047981:arginyl-glycyl-aspartic acid