Researchers at the University of Chicago have found a way to combine cancer chemotherapy with gene therapy designed to disrupt the growth of blood vessels to a tumor. The combination, tested in mice, is far more effective than standard chemotherapy and has no additional side effects. This innovative approach is described in the August issue of the Journal of Clinical Investigation.

This new approach evolved out of a similar system, now entering phase-2 human trials, that combines gene therapy with radiation therapy.

"The radiation therapy approach appears to be quite effective, aiming a powerful anticancer arsenal at the tumor," said Ralph Weichselbaum, M.D., professor and chairman of radiation oncology at the University of Chicago and director of the study. "The new combination with chemotherapy, however, not only enables us to target the original tumor but also potentially to aim at the small clusters of cancer cells that may have spread to distant sites."

The therapy uses a modified cold virus to insert the gene for tumor necrosis factor (TNF) into cells within a tumor. TNF is a potent biological substance that can kill cancer cells directly and disrupt their blood supply, but it can be very toxic when given systemically. The researchers originally altered the TNF gene so that it could be turned on by radiation therapy. Now they have produced a version of the gene that can be activated by exposure to the common anti-cancer drug cisplatin. So mice treated with both the gene injections and cisplatin have high concentrations of TNF within the injected tumors, but nowhere else.

The researchers found that the combined therapy was far more effective than either cisplatin or TNF-gene injections alone. Tumors treated with the combination of gene therapy and cisplatin had "significant regression," note the authors, with "no additional toxicity."

Untreated tumors doubled in size within four days and grew to more th
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Contact: John Easton
jeaston@uchospitals.edu
773-702-6241
University of Chicago Medical Center
5-Aug-2002

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