New gene therapy cuts off blood supply to tumors, disrupting cancer's growth

There have been many unsuccessful attempts to disrupt cancer growth by cutting off its blood supply - until now. For the first time, researchers have developed a new gene therapy method that uses a synthetic protein to promote blood clotting, which in turn stops the blood and nutrient supply to the tumor.  The research team, led by Bradley S. Fletcher, M.D., Ph.D., an assistant professor of pharmacology and therapeutics in the College of Medicine at the University of Florida, created the "fusion protein" so that it could target another protein, TEM8 (tumor endothelial marker 8). The TEM8 protein had recently been found to be "preferentially expressed in the inner lining of tumor vessels, enabling delivery of drug molecules to the cells that harbor these proteins."

"If you can cut off the blood supply, then you can inhibit the tumor from growing," says Brad St. Croix, Ph.D., director of the National Cancer Institute's Tumor Angiogenesis Section. "The concept of targeting tumor blood vessels has been around for many years, but it's good that we're finally getting around to the stage where we can see the vessels being targeted therapeutically - it's pretty exciting," And adds team member Stephen Fernando, Ph.D., "The protein we created did a very good job of homing to the tumor and binding. By targeting TEM8, we can potentially create a therapy against cancer."

The researchers implanted mice with human colorectal cancer cells, then treated them with a gene that encodes for the artificial protein. The vehicle used to deliver the genes is a transposon called "Sleeping Beauty," a piece of DNA that can insert new genes stably and efficiently into a cell's genome. They essentially turned the lungs into a factory, which produced the protein that ultimately found its way to the target cells in the tumor vessels. Tumor volume in the treated mice decreased 53 percent and cancer cell growth slowed by 49 percent compared to the untreated mice.

The research team had successfully used the Sleeping Beauty gene delivery method in other applications, including for the treatment of hemophilia and pulmonary hypertension and the prevention of lung transplant rejection in animal studies. With success in hand, they looked for disease applications with a poor prognosis, making it worth the risk of using gene therapy. "We felt that cancer was potentially a target," Dr. Fletcher says. "Gene therapy has a lot of risk associated with it, so you don't want to do it for diseases that are not life-threatening." The findings have been published in the June 15 edition of Cancer Research.

News Release: Gene therapy technique thwarts cancer by cutting off tumor blood supply   www.healthnewsdigest.com  June 11, 2009

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