After a challenging three-year bout with a rare form of lymphoma, Chris Christiansen's cancer was in remission and he was ready to celebrate. He booked a month-long trip through Europe in the spring of 2000, relieved that his doctors' second attempt to eliminate his disease seemed to have worked. But he was barely over his jet lag when he knew something was wrong.

"I remember getting to Zurich and feeling a bump behind my ear about the size of a pencil eraser," said the now 73-year-old Seattle resident. "By the time I got home a couple of weeks later, it was about as big as my thumb."

The best hope for a cure for Chris' relapsed disease — an unusually stubborn cancer known as mantle-cell lymphoma — was a stem-cell transplant from an unrelated adult donor. The procedure would subject Chris to heavy radiation and chemotherapy followed by an infusion of specialized blood cells. But because he was beyond the age at which transplants are typically performed, his doctors at Fred Hutchinson Cancer Research Center were reluctant to attempt the procedure for fear that he wouldn't survive the rigors of treatment.

Cancer-fighting cells

Instead, they offered him an experimental therapy developed at Fred Hutchinson that had shown promise for patients over age 50 or those medically unable to withstand a conventional transplant. Known as a mini-transplant, the procedure offered a potential cure from an unusual source: cancer-fighting immune cells harvested from a donor's blood. Chris would receive a minimal dose of radiation followed by an intravenous transfusion of donor cells. Unlike the months of hospitalization required for a typical transplant, only a few hours in an outpatient clinic would be needed for the mini-transplant. In October 2000, after a suitable donor was found, he went in for the procedure.

During the weeks after the infusion, donor immune cells — the same infection-fighting cells that help us recover from colds — would find and destroy Chris' lymphoma cells until, eventually, his disease was in complete remission. Today, three and a half years later, he remains free of cancer.

"That treatment proved to be exceptional," he said. "And the real joy of it was that I didn't have to stay in the hospital."

Power of the immune system

The mini-transplant is one of several approaches that Fred Hutchinson researchers have developed and are using with success to harness the power of the immune system as a weapon against cancer. The body's complex network of disease-fighting cells and proteins is well-known for fending off the flu and subduing strep throat. Yet scientists have discovered that the immune system also can seek out and destroy cancer cells. What's most exciting about this knowledge is that because of the immune system's exquisitely sensitive ability to discriminate between healthy and abnormal cells, immune-based treatments are much less likely to produce the painful side effects common to familiar mainstays of cancer therapy. While surgery, chemotherapy and radiation have been important weapons against cancer, they can cause considerable damage to healthy tissue.

Already, hundreds of patients have been cured of leukemia, lymphoma and other blood cancers thanks to immunotherapies pioneered by Fred Hutchinson researchers, who were among the first to recognize and tap the cancer-fighting potential of the body's natural defense system. Immune-based treatments developed at the center also hold promise for treating melanoma, ovarian cancer and other solid tumors (see adjacent sidebar). These success stories have spurred the center to embark on a major fund-raising initiative for immunotherapy research, which will accelerated the development of many more lifesaving treatments.

Overcoming evolution

But if the human immune system can fight cancer, why do people develop the disease at all? Dr. Phil Greenberg, a Fred Hutchinson researcher who was a member of the first team of doctors to successfully use immunotherapy with cloned T cells, said that our immune systems evolved mainly to protect against infectious microbes, not to rid the body of tumors. His goal is to coax the system's hidden potential into a full-blown assault against cancer.

"Cancer is a disease that predominantly affects an older population, after the reproductive age has been reached. It is only in recent times that a large percentage of people lived long enough to develop cancer," he said. "Infectious diseases historically have been major causes of death, and microbes are completely foreign to our immune systems, while cancer cells are not. Although cancer cells are abnormal, they still have many similarities to healthy cells, which makes them harder for our immune system to recognize as foreign and dangerous. Our challenge is to manipulate the system to overcome this evolutionary bias."

To understand the basis for immune-based cancer therapies, it first helps to know how the immune system hunts and kills more typical prey such as viruses, bacteria and parasites. Among the system's complex network of cells, proteins and signaling factors, two biological warriors — T cells and antibodies — deserve special mention.

T cells are white blood cells that can recognize and bind to foreign or abnormal cells. The interaction between the T-cell and its target is highly specific, much like a key fits a lock. Upon recognition of an unfamiliar or abnormal cell — like those that are cancerous or infected with a virus — the T cells trigger an immune response that blasts away the abnormal cells.

Specialized and rare

Antibodies are proteins that, like T cells, recognize and bind to foreign or abnormal invaders. This also triggers a protective immune response.

The human immune system contains a vast supply of T cells and antibodies. Each recognizes a different target, but under normal conditions there are only a few of each type of T cell or antibody present in the body. The basis for many types of immunotherapy is to find the rare cells or antibodies that recognize proteins on the surface of cancer cells and manufacture them in large quantities.

Thanks to the recent development of new techniques to study the immune system, Greenberg said that scientists now have the ability to find these cancer targets more easily than ever before. His research team has identified target proteins that already are being used to treat patients and have found many more candidates that await testing. Because cancer-cell targets may not appear quite as foreign to the immune system as a Salmonella bacterium, for example, scientists must devise ways to pump up the antitumor immune response. That challenge also can be overcome, Greenberg said.

"We know a lot more now about the factors that boost or dampen an immune response," he said. "That means we have the power to begin stepping on the gas pedal and easing up on the brakes to get the desired effect."

Greenberg's immunotherapy of choice is a technique called adoptive T-cell therapy. In the procedure, a cancer patient's T cells are extracted, and the rare ones that find and fight tumor cells are identified and stimulated to multiply. This expanded population of identical cells is then infused back into the patient, where they seek out and destroy tumor cells.

This therapy may also prove useful for treating cancers diagnosed at their earliest stages. Because T cells are so skilled at migrating to cancer cells, they may be able to wipe out a cancer even before it has developed into a detectable tumor.

Targets for cancer vaccines

T-cell therapy is helping researchers to discover the best ways to create another promising immunotherapy: cancer vaccines. Just as the immune system can be boosted by vaccination to prevent common childhood diseases like measles, preliminary research shows that vaccines may help prevent disease recurrence in cancer patients after they have gone through conventional therapy or eliminate residual tumor cells after conventional therapy is completed. Promising cancer target proteins identified and validated through T-cell therapy research will be good candidates for vaccine development, Greenberg said.

The T-cell response also underlies the curative power of the mini-transplant, developed by Dr. Rainer Storb and colleagues at Fred Hutchinson. In the procedure, patients receive a mixture of immune-system cells, including T cells, that target the cancer. Some cells in the mixture also recognize healthy cells, thus triggering an undesired immune response called graft-vs.-host disease.

Storb and colleagues are now trying to improve the cancer-fighting immune response while minimizing side effects. The work also will help researchers to adapt the mini-transplant as a therapy for solid cancers.

After his successful mini-transplant, Chris Christiansen became convinced that immunotherapy research at Fred Hutchinson is a cause worth supporting. In addition to making generous donations to support mini-transplant studies at the center, he now consults with the center's Development Department on fund-raising activities.

"I owe a great deal to the Hutch," he said. "They gave me back my life."

Read more about Lymphoma >

	2005 Patient Reunion Photo Gallery