Journal
CANCER GENE THERAPY
Volume 16, Issue 4, Pages 362-372Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/cgt.2008.80
Keywords
oncolytic adenovirus; Syrian hamster; cotton rat; biodistribution; replication; glioma
Categories
Funding
- National Cancer Institute [R01-CA122930]
- National Institute of Neurological Disorders and Stroke [K08-NS046430]
- The Alliance for Cancer Gene Therapy Young Investigator Award
- American Cancer Society [RSG-07-276-01-MGO]
Ask authors/readers for more resources
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.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available