Biodistribution of an oncolytic adenovirus after intracranial injection in permissive animals: a comparative study of Syrian hamsters and cotton rats.
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.
Sonabend
A M
AM
The Brain Tumor Center, The University of Chicago, Chicago, IL 60637, USA.
Ulasov
I V
IV
Han
Y
Y
Rolle
C E
CE
Nandi
S
S
Cao
D
D
Tyler
M A
MA
Lesniak
M S
MS
D000256:Adenoviridae / Q000235:genetics / Q000502:physiology*; D000818:Animals; D000917:Antibody Formation / Q000187:drug effects; D001921:Brain / Q000821:virology; D016543:Central Nervous System Neoplasms / Q000628:therapy; D006224:Cricetinae; D004279:DNA, Viral / Q000097:blood; D005822:Genetic Vectors / Q000008:administration & dosage / Q000493:pharmacokinetics; D005910:Glioma / Q000628:therapy; D006801:Humans; D008099:Liver / Q000821:virology; D008168:Lung / Q000821:virology; D008297:Male; D050130:Oncolytic Virotherapy / Q000379:methods; D050504:Oncolytic Viruses / Q000235:genetics / Q000502:physiology*; D051381:Rats; D013045:Species Specificity; D000637:Transaminases / Q000097:blood; D014779:Virus Replication
D004279:DNA, Viral; D000637:Transaminases