Researchers enlist immune system to kill cancer

Scientists are investigating new strategies to harness the human body's own immune system to fight skin cancer.

In a departure from the standard chemotherapy treatments, which flood patients with toxic chemicals to kill cancer cells, doctors are trying to provoke the body's natural defences to do the same thing.

Two such techniques to combat melanoma were reported in papers presented this week in Prague at a European cancer research meeting.

The strategies are the first attempts to suppress the body's T-regulatory cells, which normally keep the immune system in check. In cancer, oncologists theorize that it may be helpful for the immune system to remain active, thereby unleashing it on the cancer.

"This is a fundamentally different approach to treating cancer," said Dr. Alexander Eggermont, professor of surgical oncology at the University of Rotterdam, Netherlands, the conference's chairman. Eggermont was not connected to either of the skin cancer research papers.

While the research is still preliminary, the scientists' novel approach to attacking cancer has already produced some promising results.

In a paper presented by Dr. Jason Chesney of the JG Brown Cancer Center in Kentucky, seven patients with advanced skin cancer were given a drug combination of diphtheria toxin and interleukin 2, intended to knock out the body's T-regulatory cells. In five of the seven patients, tumours shrank or remained stable.

By wiping out the T-regulator cells, the drug prevented the immune system from shutting down, thus priming the body to mount a continuous attack against cancer, Chesney explained.

Encouraging results

"This is a landmark study," said Dr. Anna Pavlick, director of the melanoma program at New York University Medical Center's Cancer Institute, who was not involved in the study. "What it shows is that by suppressing T-regulatory cells, we can take the brakes off a patient's immune system."

Though Pavlick says it's too early to change how patients are treated based on Chesney's study alone, she believes the methodology merits further research.

"It's like having permanent chemotherapy," said Chesney. "You're inducing your own immune system to stick around and keep this cancer from growing."

Advanced melanoma is a devastating disease for which there is no effective treatment. The average life expectancy is about nine months, and less than 20 per cent of patients survive more than two years after diagnosis.

Enlisting antibodies

In another study presented Wednesday, Dr. Jeffrey Weber, a professor of medicine at the University of Southern California in Los Angeles, described how he and colleagues were able to block a protein on T-regulatory cells, thus inhibiting them enough for the immune system to attack cancerous cells.

Patients were given shots of an antibody aimed at the T-regulatory cells. Out of 25 patients tested, 24 are alive after 17 months, and three are free of cancer.

If this strategy of manipulating the immune system proves successful, the whole framework of cancer treatment might be changed.

Until recently, chemotherapy was thought to be the best way to eliminate tumours. Yet while chemotherapy certainly reduces the size of tumours, it cannot prevent their recurrence and is only a short-term solution.

Risks outweighed

"If we can change the rules of the game by keeping the immune system active, we might be able to prevent tumour regrowth," said Eggermont.

Allowing the immune system to run wild does not come without risk; doctors admit it could lead to autoimmune diseases including hepatitis, colitis or dermatitis. Still, most say those conditions are manageable and are outweighed by the prospect of beating skin cancer.

Earlier this year, scientists at the U.S. National Cancer Institute used a similar technique, turning regular red blood cells into cancer-killing agents.

That involved genetically engineering red blood cells in a laboratory and artificially producing billions more of them before re-injecting them into patients.

But the strategies employed by Chesney and Weber are far more straightforward, as they don't involve genetic manipulation in a laboratory.

More data needed

Both Chesney and Weber say it will be years before their strategies are sufficiently tested to know if they work on a wide scale.

But if their hypotheses prove correct, they could also be applied to other types of cancer in which T-regulatory cells are known to play a role, such as breast, kidney or esophageal cancer.

"This is how successful therapies get started," said Dr. Rick Bucala, a professor at Yale University's School of Medicine.

While Bucala says that it would be "highly significant" if the immune system could be effectively used against cancer, he cautioned there was still too little data.

"Nothing in science is meaningful until it's been replicated.