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‘Suicide Switch’ May Pave Way for Safer Cancer Therapy, Researchers Find

Cell-transplant therapies that offer promise for fighting cancer and other diseases also come with a risk: rogue cells that can turn deadly.

Now researchers at Baylor College of Medicine in Houston report on a method that engineers a so-called suicide switch into transplanted cells that, when activated with a drug, rapidly kills off the ones that cause harm. The method, tested in children undergoing stem-cell transplants to treat leukemia, wiped out the cells that turn on the body of the patient, a complication called graft-versus-host disease.

The scientists created the switch by adding a gene to transplanted cells that produces a protein causing cells to self-destruct. The switch remains dormant until doctors infuse a drug called AP1903 that activates the cell suicide. The method, described yesterday in the New England Journal of Medicine, may ultimately apply to other therapies, including embryonic stem cells, that can cause complications such as tumors.

“The issue is that cells are complex living things and sometimes they do something we don’t want,” said Michel Sadelain, an oncologist and cell therapy researcher at Memorial Sloan-Kettering Cancer Center in New York, who wrote an editorial accompanying the study, in a telephone interview. “If you want to get rid of them, this study reports a very remarkable novel approach.”

The suicide switch is activated by a single dose of an otherwise inert drug. In four children with leukemia who started to develop graft-versus-host disease after getting transplanted immune system cells from bone marrow, one infusion of the drug killed more than 90 percent of the rogue cells in just 30 minutes, the researchers reported. It stopped the graft-versus- host disease.

Control Mechanism

With transplanted cells, “you have to have a mechanism where you can control them,” Malcolm K. Brenner, a hematologist at Baylor College of Medicine, and senior author on the study, said in a telephone interview. The new suicide switch “is a much faster and more effective control mechanism than we have had up until now.”

The suicide switch has worked in various types of stem cells in test-tube studies his team has conducted, Brenner said.

Bone marrow transplant is a method used to treat leukemia and other types of cancer by wiping out diseased bone marrow cells with drugs and radiation and transplanting in new bone marrow cells from a donor.

Partial Match

Unlike conventional bone marrow transplants using matched donors, in this study the Baylor College of Medicine researchers were treating kids with leukemia using cells from donors that were only a partial match to the children receiving them, increasing the risk of side effects such as graft-versus-host disease. To mitigate the complication, the researchers added the suicide gene to T-cells, a type of immune system cell that was transplanted into the patients.

Bellicum Pharmaceuticals Inc., a closely held company in Houston, has commercial rights to the technology used in the Baylor study. It plans to begin human studies in graft-versus- host disease in 2012, said Brad Miles, a spokesman for the company, in an e-mail. Graft-versus-host disease is a well-known and potentially lethal complication of bone marrow transplants in which transplanted cells attack the patient’s body.

To contact the reporter on this story: Robert Langreth in New York at rlangreth@bloomberg.net;

To contact the editor responsible for this story: Reg Gale at rgale5@bloomberg.net

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