Adenovirus-mediated delivery of antiangiogenic genes as an antitumor approach
| Autor: | Martine Marigliano, Dominique Roecklin, Valérie Calenda, Yves Poitevin, Stéphane Paul, Gilles Cauet, Etienne Régulier, Jacqueline Kintz, Catherine Ledoux, Horst Homann |
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| Rok vydání: | 2001 |
| Předmět: |
Cancer Research
Angiogenesis Genetic Vectors Melanoma Experimental Angiogenesis Inhibitors Biocompatible Materials Pregnancy Proteins Gene delivery Adenoviridae Neovascularization Mice In vivo Tumor Cells Cultured medicine Animals Humans Rats Wistar Molecular Biology Fibrin Neovascularization Pathologic business.industry Melanoma Gene Transfer Techniques Genetic Therapy Neoplasms Experimental medicine.disease Peptide Fragments In vitro Endostatins Rats Chemokine CXCL10 Endothelial stem cell Drug Combinations Cancer research Molecular Medicine Fibroblast Growth Factor 2 Proteoglycans Collagen Endothelium Vascular Laminin medicine.symptom Endostatin business Chemokines CXC |
| Zdroj: | Cancer Gene Therapy. 8:45-54 |
| ISSN: | 1476-5500 0929-1903 |
| DOI: | 10.1038/sj.cgt.7700278 |
| Popis: | Based on the observation that the growth of solid tumors is dependent on the formation of new blood vessels, therapeutic strategies aimed at inhibiting angiogenesis have been proposed. A number of proteins with angiostatic activity have been described, but their development as therapeutic agents has been hampered by difficulties in their production and their poor pharmacokinetics. These limitations may be resolved using a gene therapy approach whereby the genes are delivered and expressed in vivo. Here we compared adenoviral delivery of endostatin, proliferin-related protein (PRP), and interferon-inducible protein 10 (IP10) genes. Recombinant adenoviruses carrying the three angiostatic genes express biologically active gene products as determined in vitro in endothelial cell proliferation and migration assays, and in vivo by inhibition of neoangiogenesis in rat chambers. Eradication of established tumors in vivo, in the murine B16F10 melanoma model in immunocompetent mice, was not achieved by intratumoral injection of the different vectors. However, the combination of intravenous plus intratumoral injections allowed rejection of tumors. Ad-PRP or Ad-IP10 were significantly more efficient than Ad-endostatin, leading to complete tumor rejection and prolonged survival in a high proportion of treated animals. These data support the use of in vivo gene delivery approaches to produce high-circulating and local levels of antiangiogenic agents for the therapy of local and metastatic human tumors. |
| Databáze: | OpenAIRE |
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