期刊
GENE THERAPY
卷 16, 期 12, 页码 1405-1415出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/gt.2009.97
关键词
adenovirus; capsid engineering; aminopeptidase N; integrin; angiostatin
类别
资金
- CNRS
- Association pour la Recherche contre le Cancer (ARC)
- Ministere de la Recherche et de la Technologie
- Societe Francaise du Cancer
- ARC
- Association Francaise contre les Myopathies
- Societe Francaise d'Hematologie
Adenovirus (Ad)-mediated delivery of anti-angiogenic molecules into tumors constitutes an appealing approach for growth inhibition. However, lack of expression on tumors of Ad receptors leads to weak tumor transduction. Therefore, to provide Ad with a new entry pathway into tumors, an NGR peptide was inserted into either fiber (AdFNGR) or hexon (AdHNGR) capsid proteins. This strategy provided Ad with a very efficient entry pathway in both endothelial cells and tumor cells, with the highest efficacy observed for AdHNGR. Using pharmacological, biochemical and genetic approaches, AdHNGR and AdFNGR were shown to bind not only to CD13 receptor, but also to alpha v beta 3 integrins. Both vectors were efficient tools to deliver angiostatin K1-5 cDNA into endothelial cells, thus leading to a dramatic inhibition of their proliferation and increased cell death. Although AdHNGR and Adwt were found to display similar gene transduction efficacy in Lewis lung carcinoma (LLC), pseudotyping AdHNGR with an Ad3-fiber unmasked the ability of NGR-peptide to target these tumors. As a result, delivery of angiostatin K1-5 cDNA into highly aggressive tumors translated into a stronger inhibition of their growth. Altogether, our results suggest that NGR-bearing Ad are valuable tools to realize the potential of this anti-angiogenic approach to anti-tumor therapy. Gene Therapy (2009) 16, 1405-1415; doi: 10.1038/gt.2009.97; published online 30 July 2009
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