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Gene therapy gives hope to brain patient

Saturday, July 08, 2000

By Christopher Snowbeck, Post-Gazette Staff Writer

Italo Cappabianca has brain cancer, but that hasn't slowed him down much. He's continued his work in the state's House of Representatives, he's contemplating a run for mayor of his hometown of Erie and he has plans to visit Sicily this fall.

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There's another trip Cappabianca has plans for.

"I keep telling these guys, we're going for the Nobel Prize in medicine for this -- at least a nomination -- and we'll all go to Sweden together," he said.

Cappabianca yesterday became the first person to receive an experimental gene therapy treatment at the University of Pittsburgh Cancer Institute that could work like a vaccine against malignant glioma, a cancer of brain cells that hits 17,000 Americans every year.

Dr. Hideho Okada made five injections of the vaccine into Cappabianca's upper left leg. Okada and Dr. Frank Lieberman, both of the cancer institute, are the "guys" that Cappabianca hopes to escort to Sweden once the vaccine cures him of his disease.

The odds aren't in his favor.

Cappabianca, 62, was diagnosed with brain cancer last summer. The cancer came back this spring, which means the loquacious Democrat is facing odds that he might not live to see the 2001 election season. His doctors say that patients with his type of brain cancer live an average of 6 to 9 months after recurrence.

But that's not how Cappabianca sees it.

When asked about the future, Cappabianca says: "I think of success -- I think of a cure."

It's been a controversial year in the world of gene therapy. At a time when scientists have announced the successful decoding of much of the human genome and observers have speculated on the future for genetic medicine, gene therapy projects like the one Cappabianca is enrolled in are under more scrutiny than ever.

The federal government shut down the gene therapy program at the University of Pennsylvania in January after the September death of an 18-year-old patient.

It was the first fatality attributed to the controversial field of medicine.

When Cappabianca heard about the controversy, he was scared -- not of going forward with his treatment, but that his experimental treatment would be shut down before it even began.

Luckily, that didn't happen. Okada said UPCI researchers have maintained good relations with the Food and Drug Administration in the wake of the Penn controversy to make sure the local research project could continue safely and speedily.

The project is called a Phase I trial, meaning it seeks to show that a proposed treatment doesn't harm patients. To develop the brain cancer vaccine, doctors removed part of Cappabianca's tumor in April and multiplied some of the cells for several weeks in a laboratory culture.

Using a specially engineered virus, the researchers then inserted three genes into his fibroblasts, cells that serve as connective tissue. One of the genes produces an immune system stimulator called interleukin-4. Another makes an enzyme called thymidine kinase, which makes the cells vulnerable to being killed by a drug called gancyclovir, and the third gene produces a marker protein that makes the cell easy to find.

The scientists used the marker gene to locate and then isolate the fibroblasts infected with the virus-gene combination. Those modified cells, along with some of his tumor cells that were irradiated to prevent them from multiplying, made up the vaccine given to Cappabianca yesterday. The idea is that interleukin-4 will stimulate an immune system response to the tumor cells, causing the immune system to seek and destroy other tumor cells.

Eight days after the injection, the doctors will administer gancyclovir, which will kill off the vaccine cells as a safety precaution.

Cappabianca will spend much of the next month in Pittsburgh receiving treatments. But doctors won't know for at least two weeks if the vaccine has had any effect on his immune system. And even if the immune system does respond, it won't be clear for another two weeks what impact it will have on his disease. Doctors will use MRI scans at 30 days and 90 days to check whether the vaccine is fighting the brain cancer.

Cappabianca will visit the hospital often during his time in Pittsburgh, but he will spend much of the time at the house of a sister who lives in Bellevue. Two of his siblings, his wife and his brother's wife were with the politician during the injection yesterday.

"I'm looking out to help myself, obviously, but at the same time there's a possibility I can help some other people," he said. "You've got to be adventurous, you've got to be bold. You've got to go where no one else has gone before, like they say in that starship. They're going to learn something from me one way or another."

UPCI researchers are not looking to enroll another patient in the study until they've had time to monitor Cappabianca's progress.

Still, anyone interested in getting information about the research project can call UPCI at 1-800-237-4724.

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