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Gene Therapy Plus Radiotherapy Delays Esophageal Cancer Growth in Mice

Gene Therapy Plus Radiotherapy Delays Esophageal Cancer Growth in Mice

WASHINGTON—Combining gene therapy with radiotherapy may provide a
useful approach to combating human esophageal cancers, said Vinay Kumar Gupta,
MD, of the University of Chicago Medical School, at the 54th Annual Cancer
Symposium of the Society of Surgical Oncology.

The experimental approach uses a recombinant adenovirus designed to express
tumor necrosis factor-alpha (TNF-alpha) under the regulation of Egr-1, a
promoter gene sensitive to ionizing radiation, Dr. Gupta said.

The researchers hypothesized that infecting a tumor with the adenovirus
(Ad.Egr.TNF-alpha, produced by Gen-Vec, Gaithersburg, Md) and then exposing it
to radiation would produce TNF-alpha, which, in turn, would slow down the tumor’s
growth. In a sense, he said, tumors infected with the TNF-alpha-producing virus
would contain "suicide genes."

To test their hypothesis, the researchers injected human esophageal
adenocarcinoma into the legs of nude mice. After the tumors had grown to 250
mm², the mice were randomly assigned to four different treatments: injections
of the recombinant virus followed by ionizing radiation to the tumor area;
injections of the virus but no radiation; a viral buffer plus radiation; and
viral buffer alone.

Tumors treated with the virus but not radiation did express TNF-alpha at low
levels, Dr. Gupta reported, but the addition of radiation increased TNF-alpha
levels by 36-fold. No TNF-alpha appeared in either of the groups that did not
receive the virus.

Growth of the tumors treated with the combined therapy was significantly
delayed, compared with the other three groups, with no added toxicity, Dr.
Gupta said.

Although there is no solid proof that reducing the size of esophageal
cancers increases patient survival, Dr. Gupta found these results particularly
encouraging because, he said, the location of human esophageal cancer makes it
treatable by injection.

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