A gene transfer comparative study of HSA-conjugated antiangiogenic factors in a transgenic mouse model of metastatic ocular cancer

• Published in: Cancer gene therapy Vol. 14; no. 3; pp. 251 - 261
• Main Authors: Frau, E, Magnon, C, Opolon, P, Connault, E, Opolon, D, Beermann, F, Beerman, F, Abitbol, M, Perricaudet, M, Bouquet, C
• Format: Journal Article
• Language: English
• Published: England Nature Publishing Group 01-03-2007
• Subjects: Activating Transcription Factors - genetics; Adenoviridae - genetics; Adenoviruses; Angiogenesis; Angiogenesis Inhibitors - genetics; Angiogenesis Inhibitors - therapeutic use; Angiostatin; Angiostatins - genetics; Animals; Blood Proteins - genetics; Brain Neoplasms - genetics; Brain Neoplasms - secondary; Brain Neoplasms - therapy; Care and treatment; Collagen Type IV - genetics; Endostatin; Endostatins - genetics; Epithelium; Eye cancer; Eye Neoplasms - genetics; Eye Neoplasms - pathology; Eye Neoplasms - therapy; Gene therapy; Gene transfer; Gene Transfer Techniques; Genetic aspects; Genetic Therapy; Genetic transformation; Genetic Vectors - genetics; Health aspects; Human serum albumin; Humans; Metastases; Metastasis; Methods; Mice; Mice, Nude; Mice, Transgenic; Neovascularization, Pathologic; Peptide Fragments - genetics; Physiological aspects; Retina; Rodents; Serum Albumin - genetics; Simian virus 40; Survival Rate; Transgenic mice; Tumor Cells, Cultured; Tumors; U-Plasminogen activator; Urokinase-Type Plasminogen Activator - genetics; France
• ISSN: 0929-1903; 1476-5500
• DOI: 10.1038/sj.cgt.7701005

Different antiangiogenic and antimetastatic recombinant adenoviruses were tested in a transgenic mouse model of metastatic ocular cancer (TRP1/SV40 Tag transgenic mice), which is a highly aggressive tumor, developed from the pigmented epithelium of the retina. These vectors, encoding amino-terminal fragments of urokinase plasminogen activator (ATF), angiostatin Kringles (K1-3), endostatin (ES) and canstatin (Can) coupled to human serum albumin (HSA) were injected to assess their metastatic and antiangiogenic activities in our model. Compared to AdCO1 control group, AdATF-HSA did not significantly reduce metastatic growth. In contrast, mice treated with AdK1-3-HSA, AdES-HSA and AdCan-HSA displayed significantly smaller metastases (1.19+/-1.19, 0.87+/-1.5, 0.43+/-0.56 vs controls 4.04+/-5.12 mm3). Moreover, a stronger inhibition of metastatic growth was obtained with AdCan-HSA than with AdK1-3-HSA (P=0.04). Median survival was improved by 4 weeks. A close correlation was observed between the effects of these viruses on metastatic growth and their capacity to inhibit tumor angiogenesis. Our study indicates that systemic antiangiogenic factors production by recombinant adenoviruses, particularly Can, might represent an effective way of delaying metastatic growth via inhibition of angiogenesis.