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Cancer treatment uses 'suicide' gene.

An unforeseen marriage between gene-transfer experiments and chemotherapy may offer safer human gene therapy and a potent anticancer weapon, researchers say.

On July 29, the National Institutes of Health Human Gene Therapy Subcommittee provisionally approved the experimental injection of 16 ovarian cancer patients with drug-sensitive tumor cells. Scott M. Freeman and his colleagues at the University of Rochester (N.Y.) Medical Center expect final approval for this anticancer trial within eight months.

Freeman's group plans to incorporate the thymidine kinase (tk) gene, isolated from the herpes simplex virus, into cultured human tumor cells. The enzyme this gene codes for plays an integral role in DNA synthesis and cell reproduction. Because the tk gene is sensitive to the antiviral drug ganciclovir, injecting patients with cells incorporating this gene should render their tumors susceptible to ganciclovir.

Freeman's team was surprised to find that when tumor cells carrying the tk gene were injected into mice, ganciclovir killed not only the newly added cells but also existing cancer cells. The exact mechanism remains unclear, but tk-negative cells might become tk-positive by absorbing fragments of the killed cells, Freeman says. There might also be a tumor-attacking immune response from ganciclovir's actions, he adds.

In the July issue of New Biologist, Elizabeth Nabel and her colleagues at the University of Michigan Medical Center in Ann Arbor propose a different use for the tk gene: including this "suicide" gene along with any other therapeutic gene to be incorporated by the body.

Any new genes added to the body carry with them some chance of triggering uncontrolled cell growth, although such tumors have not yet been seen in treated animals. Growth factor genes, which one day may fight cardiovascular disease by spurring blood vessel growth, cause particular concern, says Nabel.

Inserting the tk gene along with the new gene could provide an off-switch to the experimental therapy. "If you saw a tumor was growing, you might give the patient ganciclovir" and selectively kill the newly added cells and their progeny, Nabel says. In mice, ganciclovir eliminated most tumors spawned by injected tk-positive cancer cells, she reports.

The tk gene could serve as a safety feature, much like the brakes in a car, says Nabel. Human gene therapy has not yet needed such a measure. However, she argues, "the ability to regulate recombinant gene expression will become increasingly important."
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Title Annotation:thymidine kinase gene developed as therapy
Author:Travis, John
Publication:Science News
Date:Aug 3, 1991
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