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In vivo imaging of adenovirus transduction and enhanced therapeutic efficacy of combination therapy with conditionally replicating adenovirus and adenovirus-p27
Cited 19 time in
Web of Science
Cited 20 time in Scopus
- Authors
- Issue Date
- 2006-01-07
- Publisher
- American Association for Cancer Research
- Citation
- Cancer Res. 2006 Jan 1;66(1):372-7.
- Keywords
- Adenoviridae/genetics/*physiology ; Animals ; Cyclin-Dependent Kinase Inhibitor p27/biosynthesis/*genetics ; Gene Expression ; Gene Therapy/*methods ; Humans ; Luciferases/biosynthesis/genetics ; Luminescent Measurements ; Lung Neoplasms/genetics/metabolism/*therapy/virology ; Mice ; Transduction, Genetic ; Virus Replication ; Xenograft Model Antitumor Assays
- Abstract
- Gene therapy is hampered by poor gene transfer to the tumor mass. We previously proposed a combination adenoviral gene therapy containing a conditionally replicating adenovirus (CRAD) expressing mutant E1 (delta24RGD) and a replication-defective E1-deleted adenovirus to enhance the efficiency of gene transfer. Mutant E1 expressed by delta24RGD enables the replication of replication-defective adenoviruses in tumors when cancer cells are co-infected with both viruses. In this study, gene transfer rates in xenografts tumors were monitored by bioluminescence in cells infected with the replication-defective adenovirus-luciferase (ad-luc). Tumor masses treated with CRAD + ad-luc showed dramatically stronger and more prolonged luciferase expression than ad-luc-treated tumors and this expression spread through the entire tumor mass without significant systemic spread. Transduction with CRAD + replication-defective adenovirus-p27 increased the expression of p27 by 24-fold versus transduction with ad-p27 alone. Treatment of a lung cancer cell line and of established lung cancer xenografts with CRAD + adenovirus-p27 also induced stronger growth suppression than treatment with either virus alone. These findings confirm the selective replication of E1-deleted adenovirus containing a therapeutic gene due to the presence of mutant E1 produced by delta24RGD in tumors. Moreover, this replication increased the therapeutic gene transfer rate and enhanced its antitumor effects.
- ISSN
- 0008-5472 (Print)
- Language
- English
- URI
- http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=16397251
https://hdl.handle.net/10371/28252
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