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Blood Clots Induced by Gene Therapy Block Cancer Growth

By LabMedica International staff writers
Posted on 25 Jun 2009
Cancer researchers working with a mouse model of human colorectal cancer have demonstrated the efficacy of a gene therapy treatment that targets a protein preferentially expressed by the endothelial cells that line the tumor's vascular system.

Investigators from the University of Florida (Gainesville, USA) created a "fusion protein” that specifically targets a protein called tumor endothelial marker 8 (TEM8), which is preferentially expressed in the inner lining of tumor blood vessels. More...
Binding of the fusion protein to TEM8 causes the formation of a clot that blocks the blood vessel and prevents nutrients and oxygen from reaching the tumor.

In an article published in the June 2, 2009, online edition of the journal Cancer Research the investigators described how they used the "Sleeping Beauty” transposon technique to introduce the fusion protein gene into a mouse xenograft model of human colorectal carcinoma.

Results of the study revealed that in the treated mice tumor volume decreased 53% and cancer cell growth slowed by 49% compared with the untreated animals. Immunohistochemistry confirmed tumor endothelial expression of TEM8, fusion protein homing to tumor vasculature, decrease in vessel density, and localized areas of thrombosis.

"We felt that TEM8 was an ideal target because it was inside the vessel, preferentially expressed there and unique,” explained senior author Dr. Bradley S. Fletcher, assistant professor of pharmacology and therapeutics at the University of Florida. "We felt that cancer was potentially a target. Gene therapy has a lot of risk associated with it, so you do not want to do it for diseases that are not life-threatening.”

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