Katja[a]
Intra-arterial delivery of endostatin gene to brain tumors prolongs survival and alters tumor vessel ultrastructure
F H Barnett1, M Scharer-Schuksz1, M Wood1, X Yu2, T E Wagner2 and M Friedlander1
1Department of Cell Biology, The Scripps Research Institute, La Jolla, CA, USA
2The Oncology Research Institute, Greenville Hospital System, Greenville, SC, USA
Correspondence to: Dr M Friedlander, Department of Cell Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, MB28, La Jolla, CA 92037, USA
Abstract
Glioblastoma multiforme (GBM) is an incurable malignant brain tumor, usually fatal within 1 year of diagnosis. Using a syngeneic rat 9L gliosarcoma model, we have developed a novel drug delivery method in which naked plasmid DNA is selectively targeted to brain tumors via intra-arterial injection. Using a plasmid encoding the antiangiogenic endostatin, transgene expression can be detected in tumor cells in vivo, and therapeutic efficacy is observed. Administration of this plasmid resulted in an 80% tumor volume reduction 1 week after treatment and enhanced survival time by up to 47%. Treated tumors exhibited a 40% decrease in the number of tumor vessels; ultrastructural analysis of remaining tumor vessels demonstrated a number of changes including markedly narrowed or collapsed lumens. We conclude that intra-arterial injection of plasmids selectively targets therapeutic genes to CNS neoplasms. This method of gene therapy holds promise for the treatment of these highly malignant brain tumors.
Gene Therapy (2004) 11, 1283-1289. doi:10.1038/sj.gt.3302287
Published online 27 May 2004