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Killing tumors with fewer side effects.

For nearly two decades, biomedical researchers have known that the body produces a substance called tumor necrosis factor CrNF) that can fight -- and sometimes kill - cancers. However, attempts to treat cancer patients with extra TNF have been unsuccessful because amounts of the substance large enough to combat tumors can also cause dramatic weight loss and throw patients into potentially fatal shock.

Now, a team of European scientists has discovered a mutant form of TNF that can kill cancer cells without causing such serious side effects. Walter Fiers of the University of Ghent in Belgium and his colleagues have found that the mutant TNF binds to only one of two types of TNF receptors on body cells.

Fiers and his co-workers report in the Jan. 21 NATURE that the mutant, TNF binds to receptors that prompt immunesystem cells to attack tumors. However, the substance fails to bind to receptors responsible for triggering a toxic reaction.

The researchers have also demonstrated that the mutant TNF can kill cancerous human cells that have been transplanted into experimental animals. They found that injections of mutant TNF plus another cancer-fighting substance called gamma interferon could eradicate human tumors from experimental mice without causing harmful side effects. The treatment "almost completely inhibited growth of the [tumors], and some animals were apparently cured," Fiers' group observed.

The combination of modified TNF and interferon offers promise as a new cancer treatment, says Frances Balkwill of the Imperial Cancer Research Fund in London. "If the complexity and toxicity of [TNF's] action can be restricted by the use of mutant molecules... the therapeutic potential of [TNF] may be greatly increased," he writes in an editorial accompanying the new report.
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Title Annotation:mutant form of tumor necrosis factor
Author:Fackelmann, Kathy A.
Publication:Science News
Article Type:Brief Article
Date:Jan 30, 1993
Words:279
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