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Gene Therapy Technique to Be Tested in People

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WebMD Health News

June 9, 2000 (Atlanta) -- Researchers are looking for ways to use all the information that is coming out about the decoding of the human genetic system to cure many diseases. A successful gene therapy would make cancer cells their own worst enemies by causing them to produce a powerful molecule that marks the cells for destruction by the immune system.

The first human tests of the treatment are scheduled for later this year, Savio L.C. Woo, PhD, tells WebMD. Woo presented data from animal studies of the treatment here at the Department of Defense Breast Cancer Research Program Meeting.

The first patients in the study -- designed primarily to see whether the treatment is as safe in humans as it was in laboratory animals -- will be women whose breast cancer has spread to the liver. "If we validate the scientific principle that this works in the liver, there is no reason we can't deliver these genes to the other body sites where cancer has spread," says Woo, a researcher at New York's Mount Sinai School of Medicine.

The treatment uses a harmless virus to carry IL-12, a powerful human molecule that signals the immune system to attack whatever cell is carrying it. Because the virus carrying the gene is injected directly into the tumor, it can deliver a highly toxic dose of IL-12 without harming normal tissues around it.

In mice with breast cancer found in their livers, up to 40% survived after getting the IL-12 treatment, while all untreated mice died of cancer.

Even as human trials are being organized, the treatment has been improved. By adding another gene -- one that improves the functioning of part of the immune system -- the treatment becomes more than twice as effective. "We have increased long-term survival of animals from 20 to 40% to more than 80%," Woo says.

If the IL-12 gene therapy is safe in people, Woo says his team would likely seek approval for another study in which all patients would get the dose found most effective and least toxic in the first study. But in this second study, some patients also would get the additional gene.

In another conference presentation, Elieser Gorelik, MD, PhD, shows how immune therapy could improve a much-heralded new approach to cancer treatment. The therapy, called angiogenesis inhibitors, can keep tumors from growing the new blood vessels they need to survive, literally starving them to death. But these inhibitors don't work as well against some kinds of cancer as against others.

Gorelik, a researcher at the University of Pittsburgh Cancer Institute, finds that angiogenesis inhibitors are much more effective when the immune system is able to help out.

He therefore suggests that immune therapies such as IL-12 be used in combination with angiogenesis inhibitors. "Basically, the immune system is very powerful -- but not against large tumors," Gorelik tells WebMD. "The idea is to use anti-angiogenesis drugs to shrink the tumor, and then to stimulate [the immune system as a second step]."

Vital Information:

  • Scientists are working to develop a gene therapy that would mark cancerous tumors, so that they could be destroyed by the immune system.
  • The gene therapy has been tested in mice and will soon be tested in patients with breast cancer that has spread to the liver.
  • Another possible approach is to use anti-angiogenesis drugs, which shrink the tumor, in combination with immune therapies.

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