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U of M experimenting with salmonella to treat cancer

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Margaret and Fred Oakde
Margaret and Fred Oakden of Otsego, Minn. talked about Fred's participation in a clinical trial at the University of Minnesota Tuesday, March 8, 2011. Fred's cancer did not improve after receiving an experimental salmonella-based treatment. But he believes the therapy will be successful when researchers are able to give patients higher doses of the salmonella substance.
MPR Photo/Lorna Benson

After six years of battling his aggressive colon cancer, Fred Oakden reached the point where he was ready to stop battling the deadly disease.

Oakden, 69, decided he had endured enough. Then, his doctor asked if he wanted to participate in a new clinical trial using salmonella to target his tumor.

Although salmonella is a dangerous bacteria that most people try to avoid, doctors have long known that significant bacterial infections can sometimes send cancer into remission. Doctors at the University of Minnesota are experimenting with modified salmonella therapy to treat cancers in the human gut.

Early results from the clinical trial have not shown any success in reducing patient tumors. But researchers believe the treatment is very promising and that it's only a matter of time before they do succeed.

Oakden, of Otsego, was surprised by the method. But when he learned that he likely wouldn't experience any painful side effects, he thought, "why not?" His wife was less enthused. 

"Margaret almost passed out when they said salmonella," Oakden said. She had worked at the Byerly's deli for more than 20 years.

"I did almost pass out, he's absolutely right," Margaret Oakden said. "When you are trying to keep your food safe ... salmonella would be just disastrous. He said they're telling him he's going to drink it, and I'm thinking, 'Oh my word!'"

Dr. Ed Greeno
Dr. Ed Greeno, seen here in his office on March 8, 2011, is medical director of the University of Minnesota's Masonic Cancer Clinic. Greeno is leading a human cancer trial that uses modified salmonella bacteria to target cancers in the gut.
MPR Photo/Lorna Benson

University cancer researchers are experimenting with salmonella bacteria for several reasons. 

First, there's evidence that a significant bacterial or viral infection can sometimes cause cancer to go into remission. 

The idea dates back nearly 150 years. In 1868, an Austrian researcher published the first-ever report of a cancer patient who had a large tumor shrink after being exposed to a bacterial infection from another patient. The cancer patient's tumor nearly disappeared, but ultimately the patient died from the bacterial infection.

There have been similar cases in modern times where some cancer patients have responded to bacteria-based therapies. For the majority of patients though, these treatments have not been successful and they often make patients extremely sick. 

With the university's salmonella experiment, researchers weaken the bacteria to minimize the risk of an infection.

"The idea is that if we can deliver low doses of it right where the cancer is, then we can induce an immune response without making the patient real sick," said Dr. Ed Greeno, the lead investigator.

Of all the possible bacteria researchers could have tried to target colon cancer, Greeno said, salmonella was selected because it's already well adapted to the human digestive tract.

"Salmonella, when you naturally get infected with it, infects the gut, then goes into the lymph nodes and the liver and spleen," he said. "And if you think about a cancer like a colon cancer, it starts in the wall of the colon, it goes into the lymph nodes and spreads into the liver. So we're taking a bacteria that follows that path naturally."

The researchers knew that salmonella alone, especially a weakened form of the bacteria, probably wouldn't be enough to rev up a patient's immune response. So they added a protein to the bacteria that searches for infections and alerts the body's immune defenses when it finds them.

The protein, called Interlueken 2, is a naturally occurring substance. For some reason, though, it doesn't always find its way to cancerous tumors on its own. By having the protein hitch a ride on the salmonella, Greeno's team hopes the treatment will deliver a more potent attack against cancer.

When the experimental therapy was given in high doses to mice with colon cancer, Greeno said, the results were amazing.

"With one dose you would see a 50 to 75 percent reduction in the volume of tumor in their liver," he said.

When the Phase 1 human trial started late last summer, Oakden was the sixth patient to qualify. In August, he received a single, low dose of the treatment to see if it was safe in humans. Oakden didn't develop any side effects. He also didn't see any improvement in his cancer. 

"There was no effect at all. We're in Phase 1 and the dosage rate is very, very low at this stage of the game," Oakden said. "You catch yourself wondering, 'Why couldn't I have just held off until Phase III or whatever the magic number is farther down the line?' But maybe we helped a little bit there. You know, somebody had to be on the front end."

Of the dozen patients treated so far, Greeno said, none has shown any improvement in their cancer.

"It is disappointing," he said. "It's not unexpected though."

Greeno said a benefit probably won't be detected until patients are given much stronger doses of the salmonella treatment — similar to the dosages given to mice in earlier studies. That phase of the project is still many months away. 

Oakden would gladly offer to take part in that research. But after participating once, he is no longer eligible for additional phases of the trial.