II. NON-TECHNICAL ABSTRACT 
Gene Therapy of Malignant Mesothelioma 
Non-Technical Abstract 
This protocol is designed to develop a new approach for the treatment of a type of chest tumor 
called pleural mesothelioma. This is a malignant tumor of the lining cells of the lungs that is 
strongly linked to prior asbestos exposure. At present, the disease is uniformly fatal- with a 
life-expectancy at time of diagnosis of about one to one and a half years. Although trials of 
radical surgery and chemotherapy have been conducted, none have shown much promise or 
efficacy. Clearly there is a need for new treatment approaches. 
One of the most exciting new approaches to cancer treatment is gene therapy. This strategy 
involves inserting a specially designed “gene” into cancer cells. Once inside the cancer cell, this 
gene becomes the blueprint for the production of a new protein which can be used to help destroy 
the cancer. 
Our approach to gene therapy is to place a "suicide" gene into a type of common-cold virus (the 
adenovirus) and infect tumors with the modified virus. In preliminary experiments, we have 
found that this virus efficiently infects tumor cells and makes them sensitive to an anti-viral 
drug (called ganciclovir) that does not harm humans or animals. 
We have developed animal models of mesothelioma by injecting tumor cells into mice and rats. 
In these animals, the tumors grow rapidly causing death within 4-6 weeks. In animals with 
growing tumors, injection of the modified virus followed by treatment with the drug ganciclovir, 
has cured 80% of the animals and markedly reduced the tumor burden in the remainder. 
Based on these observations, we propose to use this gene therapy strategy in patients with 
mesothelioma by injecting the modified virus directly into the chest cavity (near the tumors) 
and then treating the patients with the drug ganciclovir. In the first trial, the safety of using 
this system will be determined. Each subject will be carefully observed for any signs of 
infection, irritation, or other adverse effects. Successful completion of this project would pave 
the way for additional studies aimed at effectively treating, and hopefully curing, patients with 
this form of cancer. 
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Recombinant DNA Research, Volume 20 
