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Early trial data suggest gene therapy could extend lives of mesothelioma patients

About 80 percent of mesothelioma patients enrolled in a clinical trial that combines gene therapy with chemotherapy have shown improvement, the study’s lead investigator says.


Daniel Sterman, associate professor of medicine at the University of Pennsylvania Medical Center, said in a teleconference sponsored by the Mesothelioma Applied Research Foundation that the “very preliminary” results represent a dramatic improvement over the 40 percent response rate for chemotherapy alone.


The study, conducted at Penn’s Abramson Cancer Center, began a year ago. The patients, adults diagnosed with pleural mesothelioma, are treated with pemetrexed-cisplatin, the standard chemotherapy regimen for mesothelioma patients, and injections of the interferon-alpha gene.


Fifteen patients are currently enrolled in the Phase II trial, with three more to be added next month. Sterman said he plans to present the preliminary data later this year.


“We are so excited about where we are now,” Sterman said. “We have been trying for almost 18 years to bring gene therapy closer to what would be called mainstream treatments for mesothelioma.”


Gene therapy — identifying and repairing defective genes to treat disease — has been evolving for more than 20 years. The most common therapy involves using DNA from a patient’s own cells to create a healthy gene to replace one that has mutated.


Sterman said Penn has focused much of its gene therapy research on mesothelioma

patients. The university is in Philadelphia, a former shipbuilding hub that Sterman calls a “hotbed for the disease.” Since 1979, Pennsylvania has had one of the country’s highest rates of asbestos-related death and illness, according to the Centers for Disease Control.


The first clinical trials of gene therapy for mesothelioma at Penn took place in 1995, and were limited to patients who had exhausted or rejected other forms of therapy. Two patients lived for more than 10 years, Sterman said — a startling outcome for an incurable disease that typically kills a patient within six to 18 months of diagnosis.


Sterman said one patient who was treated with single dose of gene therapy in 1998 is “still alive and doing well” in Australia.


“What we learned from these early trials was the safety of the technique,” he said. “We learned how to deliver it, how to evaluate patients, how to look for responses, how to determine whether the gene we were delivering was activated and delivering the proteins it was supposed to produce.”


Early data from Phase II suggest that, once the interferon-alpha gene is injected into the patient’s chest cavity, it triggers an immune response that attacks mesothelioma cells in other parts of the body. That means once the gene is introduced, the patient’s immune system does most of the work.


“It’s the immune cells of the patient and not the gene that travel around the body, hunt down other mesothelioma cells and start to destroy them,” Sterman said. “That’s what makes this unique.”


The ultimate goal is to develop a treatment that will “remember” what mesothelioma cells look like, enabling the patient’s immune system to fight off new tumors. If successful, Sterman said, that would transform mesothelioma “from a death sentence to a chronic disease that a patient can live with for years.”


Sterman is continuing to recruit patients for the study and hopes to have 40 by the end of the year. For now, patients will have to be treated in Philadelphia, at Abramson Cancer Center. But, he said, he and his colleagues are considering setting up trials at cancer centers in other parts of the country.


To join the trial or for more information about eligibility, call the Abramson Cancer Center at 800-789-PENN.