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Doctors take shot at cancer vaccine

Researchers in Tampa work to find a way to get the bodies of pancreatic cancer patients to fight the disease on their own.

By LISA GREENE
Published February 12, 2006

TAMPA - Sheltered between the stomach and the spine, the pancreas is the perfect hiding place to nurture one of the deadliest cancers.

Its location makes tumors harder to spot and often impossible for surgeons to operate on once they are found. This year in the United States, more than 33,000 people will be diagnosed with pancreatic cancer. More than 32,000 will die.

But doctors in Tampa dream of a day when they can help the patient's own body take action against the usually fatal disease. University of South Florida researchers have won a federal grant to design a vaccine that would stimulate the patient's immune system to kill tumors.

Creating vaccines to fight cancer is a departure from more traditional cancer treatments, such as surgery, chemotherapy and radiation. But across the country, researchers are focusing more attention on vaccines. The National Cancer Institute now is funding 290 projects that somehow involve vaccines, even though they remain experimental and none has yet been approved by the FDA.

At H. Lee Moffitt Cancer Center and Research Institute in Tampa, scientists began work on their first vaccine study about seven years ago. They now have five studies under way, with two more, including the pancreatic study, about to start.

"This is a rapidly evolving field, and it's bringing a lot of different disciplines together," said Jeffrey Schlom, chief of the laboratory of tumor immunology at the National Cancer Institute. "Unlike drugs or radiation, which are given to the patient, do their damage, and leave, what we're doing is asking the patient's own immune system to mount an attack on the cancer. It's very, very different from standard chemotherapy."

Schlom believes that in five years, two to five therapeutic cancer vaccines will have been approved by the FDA for treating patients.

"But I'm an optimist," he added.

At Tampa General Hospital, Dr. Emmanuel Zervos is staking his hopes on cancer vaccines as well. Zervos, assistant professor of surgery at the University of South Florida, is working with researchers at Moffitt on a pancreatic cancer study that has just won National Cancer Institute funding. The amount of the grant isn't final, but could be up to $750,000.

As a surgeon, Zervos knows all too well that he can't operate on most people with pancreatic cancer. He hopes that a vaccine may one day save their lives.

"That's what excites me about this trial," he said. "It's novel. It may make a difference. And it makes common sense."

* * *

Edward Jenner was the first to use a crude vaccine to fight smallpox more than 200 years ago. Since then, scientists have developed vaccines to fight off more than 20 infectious diseases, from flu to polio to rabies.

Such vaccines use weakened or dead disease cells to activate the immune system. The body reacts by producing antibodies to protect against the disease.

Most cancer vaccines are different. They are given to people who already have cancer. Their aim is not to prevent tumors, but to kill them.

"It's a little different from the concept of a measles vaccine," said William Janssen, director of the cell therapies core facility at Moffitt and one of the researchers who will work on the new study.

People always ask him, "Can I get my family vaccinated so none of them would ever get cancer?"

Janssen has to say no.

"We don't have the ability to do that with anticancer vaccines," he said. "No two cancers are ever going to be exactly alike. We can't immunize a person against cancer until they actually have that cancer."

There are a few exceptions. For example, researchers now are working on a vaccine to prevent cervical cancer. But that vaccine is more traditional. It targets the human papilloma virus, which causes cervical cancer.

The theory behind cancer vaccines takes aim at the fundamental problem of cancer. When a virus or bacterium invades the body, the immune system spots it and mobilizes to fight.

But when a malignant tumor develops, the immune system fails to recognize it. It never attacks.

"If a tumor is growing in a patient, obviously the immune system isn't combatting it," Schlom said.

Researchers believe that normally, the immune system does spot developing tumor cells and kills them. One piece of evidence, Schlom said, it that people with weakened immune systems develop more tumors.

"But the tumors that we see have developed the ability to shut down part or all of the immune system," Janssen said. "Some part of the total immune system has been turned off."

The trick is how to turn it back on.

* * *

In Tampa, researchers plan to find 35 patients with terminal pancreatic cancer - those whose tumors were found too late for surgery.

That's about 80 to 85 percent of pancreatic cancer patients, Zervos said. Most people show no symptoms until the tumor becomes big enough to block the bile duct. Then they turn yellow.

Because the pancreas is surrounded by vital organs and blood vessels, it's generally too late to operate.

"Because we see so much of this disease, we're very interested in novel treatments," Zervos said.

When the study begins later this year, patients will be treated with two therapies. They will be injected with an experimental drug designed to kill tumor cells. As those tumor cells die, they shed proteins called antigens.

Then comes the vaccine process.

Doctors remove a certain type of immune system cells, called dendritic cells, from the patient's blood. Those cells go to the lab, where Moffitt researchers grow more of them and expose them to a chemical designed to stimulate them.

The stimulation is a key step, Zervos said.

"We're trying to sort of trick the immune system into recognizing tumors they would not recognize otherwise," Zervos said.

Next, doctors will inject the dendritic cell vaccine directly into the pancreas. This step can involve passing a needle through the stomach or part of the liver. Tampa General's interventional radiologists have experience in performing this tricky procedure, which was one reason researchers could apply for the grant, Zervos said.

Doctors hope that the stimulated dendritic cells will act as couriers, taking antigens from the dying tumor cells to another kind of immune system cells, called T-cells.

Once the T-cells recognize the proteins as foreign, they can disperse and kill tumor cells throughout the body.

The mere prospect of any kind of new treatment intrigues Seminole resident Paul Ziegler. Ziegler, 55, knows too well how deadly pancreatic cancer is: His big brother, Lou, called him in October 2004 to tell him he was terminally ill.

Lou Ziegler, a North Dakota newspaper editor, had always been a clown and never been sick. So at first, Paul Ziegler thought he was joking. But his brother was dead four months later.

"It was a tough, tough fight," Ziegler said. "As a family, we just couldn't believe it was happening. He was so healthy and active, and energetic. The disease just took all of his strength."

Doctors still have obstacles to overcome in working with cancer vaccines. One difficulty now, Schlom said, is that researchers start using experimental treatments in the sickest patients - generally patients with large tumors and already weak immune systems.

But it's hard for anybody's immune system to attack a large tumor, and harder still if the immune system is already weakened.

"It's one of the dilemmas in cancer vaccines," Schlom said. "As these are shown to be safe, trials are being done in less difficult situations."

In Tampa, Zervos cautions that researchers don't expect a miracle cure for their 35 patients. While doctors would be delighted if the treatment helps these patients, they will consider the study a success if they can show that patients' immune systems did recognize tumor antigens.

Nor will the trial start right away. Even though the National Cancer Institute has agreed to fund it, researchers still need to get the study design approved by the University of South Florida and both hospitals. Though he knows there will be much interest in the study, Zervos expects it will be at least May 1 before they can start signing up patients.

But even if the trial has limited success, Paul Ziegler said, it's a step in the right direction. Right now, many families have nowhere to turn.

"The doctor called him in and said, "What you have is very serious, and it attacks very quickly, and basically, there's no hope.' It was like a death sentence," Ziegler said. Even if the vaccine didn't turn out to work for everyone, "having some kind of hope would be a gift to the families."

[Last modified February 12, 2006, 06:13:06]