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Gene Therapy For Thoracic Cancer: A Trial To Treat Malignant Mesothelioma

Investigators at the University of Pennsylvania Cancer Center have been awarded a Program Project grant from the National Cancer Institute that will help fund a novel gene therapy trial to treat patients with mesothelioma, a cancer frequently linked to asbestos exposure. These patients, upon diagnosis, usually have less than two years to live with standard mesothelioma treatment.

The trial was developed by Cancer Center members Steven Albelda, MD, Larry R. Kaiser, MD, Director of Penn's Center for Lung Cancer and Related Disorders, and Joseph Treat, MD. The protocol involves injecting a modified virus directly into a patient's chest cavity and treating the patient with an anti-viral drug that has proven effective at killing cancer cells.

This pilot trial will determine the safety of this approach. This strategy is based upon findings that cancer cells can be made susceptible to drugs when a specially designed gene is inserted into the cells. Drs. Albelda and Kaiser have been placing a suicide gene the herpes simplex thymidine kinase gene) into a common cold virus (the adenovirus), which then attacks the tumor. Preliminary experiments have found that the virus efficiently infects tumor cells and makes them sensitive to ganglicovir, an effective anti-viral drug that spares human and animal cells while killing cancer cells.

Initial experiments have focused on pleural mesothelioma, a type of chest tumor that affects the lining of the chest and is strongly linked to asbestos exposure. Mesothelioma, a relatively prevalent disease in Philadelphia and other regions where shipbuilding is a common occupation, is responsible for many deaths in exposed workers.

At present, this disease is uniformly fatal, with a mesothelioma life expectancy of 12 to 18 months from the time of diagnosis. Trials including radical mesothelioma surgery and chemotherapy have been conducted with little success.

In the thoracic oncology research laboratory at the Cancer Center, Drs. Albelda and Kaiser have developed animal models of mesothelioma by injecting tumor cells into mice and rats. Treatment of these animals with the adeno-virus containing the viralthymidine kinase gene followed by treatment with ganglicovir, the strategy proposed for the clinical setting, has cured many animals and markedly reduced the tumor burden in the remainder.

In the first clinical trial, patients will undergo this procedure and be carefully observed for any signs of infection, irritation or other adverse effects. Successful completion of this trial will lead the way for additional studies aimed at effectively treating patients with malignant mesothelioma and other thoracic malignancies.

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