Event: Teaching the body to fight cancer

Research in immunotherapies starting to pay off

by Nicky Penttila

September 29, 2006

Immunology is emerging as the "fourth weapon" in the medical fight against cancer, joining surgery, radiation and chemotherapy in the physician's arsenal, leading experts say.

Just looking at immune cells in patients' tumors can better predict the progress of the disease than looking at the tumor cells themselves, according to research published today in the journal Science. But immunologists aren't just looking.

"We are able to stimulate the immune system in ways that weren't possible before," Dr. Steven A. Rosenberg said this week at a Washington, D.C. forum, sponsored by the Dana Foundation, on how immunology is changing the treatment of cancer. In early September, he and colleagues at the National Cancer Institute reported that after they genetically modified tumor-fighting immune cells and reinserted them into people seriously ill with advanced melanoma, the cells multiplied and successfully attacked the tumors in two of their patients. Both remain cancer free more than 18 months later.

This is the first such success with people, though it is a qualified one: the other 15 gravely ill patients in the study did not improve. But the study shows that the method can work, Rosenberg and his fellow forum speakers said, and now the question is how to make it work better.

Such discoveries make immunology one of the most exciting areas in cancer treatment today, said Dr. LaSalle D. Leffall, chairman of the three-person President's Cancer Panel, which monitors the work of the National Cancer Program.

"We're using a technique that has enormous power," said Rosenberg. "Immunology is now becoming the fourth modality, the fourth weapon."

Surgery, radiation and chemotherapy will cure about half of the people who will develop cancer in 2006, Rosenberg said. That's pretty good in science terms, he noted, but bad in human terms: Around 1,200,000 people in the United States will develop an invasive (serious) cancer this year. At the current cure rate, 600,000 of those will die of it.

One-third of all Americans will develop a cancer in their lifetimes; at the current cure rate, one-sixth will die of the disease. Moreover, current treatments have serious side effects, especially radiation and chemotherapy, which deeply damage the immune system and leave already sick people open to other illnesses.

Before developing gene immunotherapies, Rosenberg said, "we were at the mercy of what the body had created," the person's faulty immune system. "We found a way to take a normal cell, use a virus to insert a gene into the cell and gave it an ability it never had before: It could recognize the cancer" and knew it needed to kill it.

Today, researchers working in France and Austria reported in the journal Science that looking at the number and types of disease-attacking T-cells near tumor cells is a better way to predict whether a patient would survive early-stage colorectal cancer than looking at the tumor itself and seeing how fast it was spreading.

The immune system is a good target for such inspection and intervention. Fighting the body's invaders is its job. But cancers often seem to stymie the system's sentinels, said Dr. Ralph Steinman, director of the Chris Browne Center for Immunology and Immune Diseases at The Rockefeller University, and another panelist at the forum. He said this may be because cancer cells change the operation of the body's own cells and are not recognized by sentinels as invaders. The sentinels then fail to sound the alarm, and the immune system's attack forces don't act.

Of all the systems in the body, the immune system is the one "you can really teach, really make better," said Steinman. "But," he added, "we don't know all the rules."

For example, in some cancers, the usual disease attackers, such as T-cells, are present in the cancer cells, but for some reason lay dormant and the disease spreads. Steinman is studying how certain sentinels, called dendritic cells, communicate with T-cells to teach them to attack cancer cells. He and his colleagues discovered and named dendritic cells in 1973.

Will these methods cure more people with cancer? It's still too early to be sure.

"We need research on humans," Steinman said. "I'm no diviner."

But research on humans is difficult, not only in performing the experiments but also in determining who may take part and who will pay for them.

Current government spending for research in immune-based treatment of cancer is roughly $250 million. That is a fraction of the $4.9 billion in total spending on cancer research, and little of that $250 million is spent on clinical trials with people, Steinman said.

Rosenberg dates the field to 1985, with the first discovery that interleukin-2 could stimulate the body's immune system to fight certain cancers. Twenty-one years is "yesterday in surgical time," he said, which helps explain why researchers, clinicians and, perhaps most importantly, dollars haven't yet matched these pioneers' enthusiasm.

Keep providing more proof and that might change, Leffall said.

He likened the status of immunotherapy to that of chemotherapy a few decades ago. Chemotherapy was first used only for the sickest patients, those for whom the other methods had failed. Now the treatment is part of the arsenal and used in tandem with surgery and radiation. Immunotherapy likely will follow the same route, he said, though it may be asked, "Is there not some role for this early on?"

Looking at where the science stands now, Leffall said, immunotherapies could well help doctors reach their common goal — to, as he put it, "have people die young as late in life as possible."