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Cancer Cure in Mice to Get Human Trials

June 29, 2008

By Zoe Elizabeth Buck, The News & Observer, Raleigh, N.C.

Jun. 29–Clinical trials begin this week at Wake Forest University on a cancer therapy that has completely cured the disease in every mouse tested over the past few years.

The therapy involves the transfusion of white blood cells from cancer-resistant donors into cancer patients, letting loose a uniquely qualified army of disease fighters to attack the invading tumor.

Some scientists are skeptical about the move from mice to humans, but others are excited about the possibility of success.

Dr. Zheng Cui, the lead investigator, and his team at the Wake Forest University School of Medicine announced the move to human clinical trials Saturday at the Understanding Aging Conference in Los Angeles. The team recently won approval for human trials from the Food and Drug Administration.

“This is the first time that such aggressive cancer in mice has been eradicated like this,” Cui said. “This is a very dramatic result.”

The result is especially dramatic considering its discovery stemmed from a series of accidents, starting with one extraordinary mouse.

In the late 1990s, Cui and his team were using mice as experimental cancer patients for their research, injecting them with malignant cells. Within three to four weeks, as expected, all the injected mice developed tumors and died.

But in 1999, for some reason, one mouse didn’t develop tumors and didn’t die.

Dr. Lloyd Old of the Ludwig Institute for Cancer Research, who was collaborating in the research, later said that if Cui had been trained as an immunologist, he would have thrown out the mouse right then. But Cui was trained as a medical doctor, and his curiosity led him to continue testing the oddball mouse, injecting it with higher and higher lethal doses of carcinogens.

No matter how many times the researchers tried to give the mouse cancer, it didn’t develop a tumor, and it didn’t die.

The mouse was immune to cancer.

Making sure

As cautious scientists, Cui and his team decided to breed the mouse and test its offspring for cancer immunity.

“We knew that if we hadn’t made a mistake, something very dramatic was happening, but we had to know we weren’t making a mistake,” he said.

It wasn’t a mistake. Three of the mouse’s seven grandchildren didn’t get cancer, either. Whatever was causing the cancer resistance was built into the mouse’s family genes. News of the finding created a stir.

“Our lives were suddenly overtaken by an unexpected media frenzy,” Cui wrote in 2003. Headlines proclaimed a cure for cancer — albeit in mice.

“People got very excited for a reason,” he said. “It was exciting. We had direct evidence for cancer immunity that we could reproduce at will. It was a very profound result, and it was not subtle. I don’t think people could have overreacted.”

The next step was to figure out how to transfer that cancer immunity from the special mice to mice that were dying of cancer. The solution is apparently hidden in the mice’s white blood cells, which are like a tiny biological army. They are carried in the bloodstream to fight infection and disease throughout the body.

For some reason — Cui and his team don’t know why — the white blood cells from the immune mice could defeat the cancer every time, while the other mice’s white blood cells were unable to stave off the infection.

The majority of contemporary cancer research focuses on these cellular soldiers. But most research seeks to isolate certain parts of the cells and stimulate them in test tubes, a complex process.

Cui’s procedure is simple.

“We don’t have to do anything to manipulate the white blood cells,” Cui said. All he and his team did was transfuse the immune mouse cells into the sick mice, and the tumors melted away.

“It’s like we discovered aspirin, only instead of curing headaches it’s curing cancer,” Cui said. “We don’t know how it works exactly, but it doesn’t really matter.”

A leap forward

Rather than spend years determining the mechanisms behind the miracle, Cui thought it was more important to press forward toward clinical trials in humans.

But Cui’s eagerness to move forward could lead to problems.

“Anything that seems like a miracle always runs into roadblocks in the future,” said Vivek Rangnekar, a cancer researcher at the University of Kentucky. “If you don’t know the mechanism behind what is going on, you will not be equipped to deal with those roadblocks. For example, they could find that the cancer builds up a resistance, and if they don’t know what’s going on they will not be equipped to deal with that.”

As Cui moves forward, he must first find a source for the cancer-fighting white blood cells — the human equivalent of that miraculous mouse.

Next week, Cui’s team will begin a search for cancer-resistant humans.

Next step: humans

Whether people are immune to cancer is probably rooted in their genetic background.

“Some families just don’t have any cancer for generations, even among heavy smokers,” he said. “Chances are it is probably not because they are lucky.”

These cancer-resistant people are identified by examining how well their white blood cells fight off cancer cells in a test tube. Once a set of donors is selected, the clinical trial will move into the treatment stage, harvesting white blood cells from immune people and transfusing them into cancer patients. The process will be relatively painless by contrast with current cancer treatments such as chemotherapy or radiation therapy, which often have debilitating side effects.

“It’s basically a blood transfusion — a safe procedure that goes on all the time,” Cui said.

Doubts and pessimism

Other researchers remain cautious. Dr. Len Lichtenfeld, deputy chief medical officer of the American Cancer Society, said it was important to note that we simply won’t know anything about the viability of the therapy for humans until the clinical trial begins.

“We’re always hopeful,” he said, “but we have to temper our enthusiasm.”

Some scientists expressed pessimism about the clinical trials. Lab mice have such close genetics that any two members of the same strain are essentially identical twins. This is not true in humans. Some experts worry that the cancer patients’ bodies will reject the donated cells from the blood transfusion, or worse, that the white blood cells, designed to identify and attack anything foreign to them, will attack the body of the patient from the inside.

Cui said he is aware that the procedure comes with risks. But, he said, the white blood cell transfusions have been used in other fields of medicine for years.

“We’ve minimized all the risk, especially for these first few rounds of trials,” he said. “We don’t know what will happen, but we hope this will cure several types of cancer and help a few people in the next months. This could be another arrow in the cancer treatment quiver.”

zoe.buck@newsobserver.com or (919) 829-4753

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