In vivo imaging of adenovirus transduction and enhanced therapeutic efficacy of combination therapy with conditionally replicating adenovirus and adenovirus-p27

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Lee, Choon-Taek; Lee, Yoon-Jin; Kwon, Sung-Youn; Lee, Jaeho; Kim, Kwang Il; Park, Kyung-Ho; Kang, Joo Hyun; Yoo, Chul-Gyu; Kim, Young Whan; Han, Sung Koo; Chung, June-Key; Shim, Young-Soo; Curiel, David T; Carbone, David P
Issue Date
American Association for Cancer Research
Cancer Res. 2006 Jan 1;66(1):372-7.
Adenoviridae/genetics/*physiologyAnimalsCyclin-Dependent Kinase Inhibitor p27/biosynthesis/*geneticsGene ExpressionGene Therapy/*methodsHumansLuciferases/biosynthesis/geneticsLuminescent MeasurementsLung Neoplasms/genetics/metabolism/*therapy/virologyMiceTransduction, GeneticVirus ReplicationXenograft Model Antitumor Assays
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.
0008-5472 (Print)
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College of Medicine/School of Medicine (의과대학/대학원)Nuclear Medicine (핵의학전공)Journal Papers (저널논문_핵의학전공)
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