Efficient delivery of angiostatin K1-5 into tumors following insertion of an NGR peptide into adenovirus capsid
| Autor: | Ronan Chaligne, Stéphane Giraudier, E. Muth, Michel Perricaudet, Céline Bouquet, Karim Benihoud, Frédéric Vigant, Betsy Jullienne |
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| Přispěvatelé: | Vectorologie et transfert de gènes (VTG / UMR8121), Université Paris-Sud - Paris 11 (UP11)-Institut Gustave Roussy (IGR)-Centre National de la Recherche Scientifique (CNRS), Institut Gustave Roussy (IGR), Bioalliance Pharma SA (Bioalliance), Laboratoire d'hématologie, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12) |
| Jazyk: | angličtina |
| Rok vydání: | 2009 |
| Předmět: |
Genetic enhancement
Integrin Genetic Vectors CD13 Antigens medicine.disease_cause Adenoviridae 03 medical and health sciences Transduction (genetics) chemistry.chemical_compound Carcinoma Lewis Lung Mice 0302 clinical medicine Capsid Transduction Genetic Cell Line Tumor Neoplasms Genetics medicine Cytokine Receptor gp130 Animals Humans [SDV.BBM.BC]Life Sciences [q-bio]/Biochemistry Molecular Biology/Biochemistry [q-bio.BM] Molecular Biology Angiostatins 030304 developmental biology 0303 health sciences Angiostatin biology Gene Transfer Techniques Lewis lung carcinoma Endothelial Cells Genetic Therapy Molecular biology 3. Good health chemistry 030220 oncology & carcinogenesis Pseudotyping Cancer research biology.protein Molecular Medicine Growth inhibition Oligopeptides |
| Zdroj: | Gene Ther Gene Ther, 2009, epub ahead of print. ⟨10.1038/gt.2009.97⟩ |
| DOI: | 10.1038/gt.2009.97⟩ |
| Popis: | International audience; 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 alphavbeta3 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 advance online publication, 30 July 2009; doi:10.1038/gt.2009.97. |
| Databáze: | OpenAIRE |
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