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Mesothelioma Treatment | Articles & Abstracts
Therapy Studies
Gene Therapy Raises Hopes...But Only Time Will Tell.
For more than five years, scientists have been trying to use gene therapy on cancer. More than 100 laboratories in 13 countries have been involved in research to find so-called "suicide genes" that would attack invading cancer cells while leaving healthy cells alone. Such is the theory behind research now being conducted at the University of Pennsylvania and involving our fellow member, Donald Hardy, the victim of mesothelioma.
Researchers at the University's Medical Center have infected cancer cells in Brother Hardy's chest with a virus or "vector," bioengineered to carry a killer gene. It is hoped that the vector has carried the gene into cancer cells making them vulnerable to an antiviral drug known as "ganciclovir", administered several days later.
In theory, the procedure is designed to fool the drug into thinking that the cancer is a viral infection and thus the drug would attack only the cancer cells, leaving healthy cells alone.
The procedure began with the insertion of a tube into Brother Hardy's chest cavity. Thoracic Surgeon Dr. Larry Kaiser then placed a syringe into the chest tube.
The syringe had been filled with "suicide genes" that were pushed into the chest cavity through the tube. Hardy, who remained conscious during the procedure, was asked to roll back and forth on the operating table so the vector would slosh up against the cancer cells.
The suicide genes make cells sensitive to the ganciclovir drug, so that when the cells containing the gene are exposed to the drug, they are killed.
"Mr. Hardy has tolerated the gene therapy very well. He is our first patient in a clinical trial that is designed to prove only the safety of this particular form of gene therapy -- which has already been shown to be safe and effective in animal models."
- Dr. Steven Albelda, principal investigator for the study
The genes, in this case are herpes simplex thymidine kinase genes, which are delivered to cancer cells via a crippled common-cold virus called an adenovirus.
Although all cells exposed to the virus take up the genes, only those cells that are rapidly dividing - such as tumor cells - are damaged by the ganciclovir. Thus, the theory is that tumor cells, not normal cells, are destroyed when the drug is given.
By way of review, the treatment is a four-step process:
- In mesothelioma, the cancer attacks the fragile membranes on the surface of the lung and the opposing chest wall. These membranes form the pleural cavity.
- To kill the cancer, researchers first insert a tube through the patient's chest wall into the cavity and inject the adenovirus.
- The injected adenovirus carries a gene that forces the pleural cells to make the enzyme thymidine kinase (TK).
- The patient is then injected with the antiviral drug ganciclovir. The drug kills only those cells making TK, thus knocking out the cancer.
Tense hours followed Brother Hardy's procedure. His temperature and heart rate increased, suggesting that perhaps the injection of killer cells had been too high. However, vital signs returned to normal and four days later biopsies were taken to determine the effectiveness of the treatment. Unfortunately, the results were inconclusive.
However, today Brother Hardy remains a picture of health - active and robust. And to some degree, he already has beaten the odds. Having been diagnosed with mesothelioma more than two years ago, he has outlived the usual prognosis for average life expectancy of no more than 18 months.
And, more importantly, there have been no signs of new tumors since his treatment. Monthly outpatient visits to the Medical Center allow doctors to continually monitor his condition and for now, so far so good.
