Biodistribution of an oncolytic adenovirus after intracranial injection in permissive animals: a comparative study of Syrian hamsters and cotton rats

• DOI: 10.1038/cgt.2008.80
• Publication Date: 2008-11-14T16:25:34Z
• Authors: A M Sonabend; I V Ulasov; Y Han; C E Rolle; S Nandi; D Cao; M A Tyler; M S Lesniak
• Keywords: Male; Oncolytic Virotherapy; 0301 basic medicine; Genetic Vectors; Brain; Glioma; Virus Replication; Adenoviridae; Rats; 3. Good health; Central Nervous System Neoplasms; Oncolytic Viruses; 03 medical and health sciences; Liver; Species Specificity; Cricetinae; Antibody Formation; DNA, Viral; Animals; Humans; Lung; Transaminases

Conditionally replicative adenoviruses (CRAds) are often evaluated in mice; however, normal and cancerous mouse tissues are poorly permissive for human CRAds. As the cotton rat (CR) is a semipermissive animal and the Syrian hamster (SH) is a fully permissive model for adenoviral replication, we compared them in a single study following intracranial (i.c.) injection of a novel glioma-targeting CRAd. Viral genomic copies were quantified by real-time PCR in brain, blood, liver and lung. The studies were corroborated by immunohistochemical, serological and immunological assays. CR had a multiple log higher susceptibility for adenoviral infection than SH. A similar amount of genomic copies of CRAd-Survivin-pk7 and human adenovirus serotype 5 (AdWT) was found in the brain of CR and in all organs from SH. In blood and lung of CR, AdWT had more genomic copies than CRAd-Survivin-pk7 in some of the time points studied. Viral antigens were confirmed in brain slices, an elevation of serum transaminases was observed in both models, and an increase in anti-adenoviral antibodies was detected in SH sera. In conclusion, CR represents a sensitive model for studying biodistribution of CRAds after i.c. delivery, allowing for the detection of differences in the replication of CRAd-Survivin-pk7 and AdWT that were not evident in SH.