Adeno-associated virus-mediated gene transfer of endostatin inhibits angiogenesis and tumor growth in vivo.
A variety of approaches has demonstrated that interfering with tumor-induced angiogenesis may be an effective strategy in cancer therapy. However, it is likely that to be most effective such strategies will require extended suppression of the angiogenic process. Gene therapy offers a possible approach to achieve sustained release of a therapeutically potent transferred gene product. In the present study the angiogenesis inhibitor endostatin was expressed through a recombinant adeno-associated viral (rAAV) vector and shown to be biologically active in vitro and in vivo. Intramuscular injection of rAAV-HuEndo (1 x 10(9) i.u.) led to a sustained serum endostatin level of approximately 35-40 ng/mL. This endostatin level was sufficient to inhibit tumor cell-induced angiogenesis and to suppress both the initiation and subsequent growth of a human colorectal cancer model.
Shi
Wenyin
W
Department of Pharmacology and Experimental Therapeutics, University of Florida, Gainesville, Florida 32610, USA.
Teschendorf
Christian
C
Muzyczka
Nicholas
N
Siemann
Dietmar W
DW
D000818:Animals; D002455:Cell Division; D002460:Cell Line; D002465:Cell Movement; D002478:Cells, Cultured; D003094:Collagen / Q000235:genetics*; D015179:Colorectal Neoplasms / Q000628:therapy; D018076:DNA, Complementary / Q000378:metabolism; D000229:Dependovirus / Q000235:genetics*; D043169:Endostatins; D004730:Endothelium, Vascular / Q000166:cytology; D018014:Gene Transfer Techniques; D005822:Genetic Vectors; D006801:Humans; D007118:Immunoassay; D007150:Immunohistochemistry; D051379:Mice; D008957:Models, Genetic; D009336:Necrosis; D009369:Neoplasms / Q000628:therapy*; D009389:Neovascularization, Pathologic; D010446:Peptide Fragments / Q000235:genetics*; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000378:metabolism; D013997:Time Factors
D018076:DNA, Complementary; D043169:Endostatins; D010446:Peptide Fragments; D019408:Platelet Endothelial Cell Adhesion Molecule-1; D003094:Collagen