Therapies Bolster

By Denise Grady

For more than 30 years, doctors have been trying to rally the weakened immune systems of cancer patients to fight the disease. Only recently, however, have therapies been developed that bring some of the body's own most potent weapons to bear in the struggle to repel invaders ranging from cancer to the AIDS virus. Those weapons include antibodies, tumor-killing blood cells and the chemical messengers that regulate them.

One promising approach is the use of interleukin-2, one of the proteins called lymphokines, which are produced by the immune system. IL-2 is now being administered in various ways to stimulate the white blood cells that attack tumors. Expensive -- upwards of $80,000 for one course of treatment -- and dangerous, IL-2 is usually reserved for patients with advanced cancer. Amy Hance, 25, of Bloomington, Ill., reached that stage early this year. Melanoma, a deadly skin cancer, had spread to her liver, spleen, stomach and lungs. The determined Hance opted for experimental IL-2 therapy, even though side effects -- including fever, massive fluid retention, anemia, nausea, vomiting, diarrhea and heart and lung problems -- had killed several patients.

At the University of Chicago's Billings Hospital, her blood was run through a machine to separate out white cells, which were incubated for several days in IL-2 to turn them into LAKs, or lymphokine-activated killer cells. The cells were then dripped back into a vein, along with IL-2. Her temperature shot up, and severe nausea set in. "I never think of the symptoms as bad, because I know there's this big fight going on in there," says Hance. Her bold gamble paid off: after 4 1/2 weeks of treatment, her tumors had shrunk by 80%.

IL-2 appears to stimulate certain immature white cells to mature into killer cells that destroy cancer. Since 1984, when the treatment was developed by Dr. Steven Rosenberg of the National Cancer Institute, more than 400 Americans have received it. Though there have been some spectacular successes, IL-2 is clearly no cure for cancer. Five percent to 10% of patients experience complete remission, and more have partial ones. But the majority reap no benefit at all. Given the expense and the risks, the treatment has come in for some sharp criticism. Even so, University of Pennsylvania Oncologist Kevin Fox notes that IL-2 therapy is the only treatment that works at all on advanced melanoma and kidney cancer. Admits Rosenberg: "It's a treatment in its infancy."

Rosenberg is working on a new and potentially more powerful therapy called TILs, for tumor-infiltrating lymphocytes. In tests on mice, he notes, these cells appear "50 to 100 times more potent than LAK." TILs are actually killer T cells that, like LAK cells, can attack cancer cells. To produce them, researchers expose malignant cells removed from the patient to IL-2. The tissue includes killer T cells that have launched a weak attack; with a sharp boost from the IL-2, they replicate and proceed to destroy the cancer. A month later, the newly potent T cells, vastly increased in number, are then infused into the patient, followed by additional IL-2.

Eight of Rosenberg's first nine patients, who had not responded to other treatments, had "good responses" to TILs. One has been in complete remission for five months. Tumors have dramatically shrunk in others, and, because patients have been exposed to IL-2 only briefly, side effects have been mild. Rosenberg is convinced that the future of cancer therapy lies in finding the right combinations of immune-system regulators, including the interleukins and interferons. Other researchers have high hopes for monoclonal antibodies that can carry drugs or radiation directly to tumors or help other immune-system cells kill the cancer cells. "Every year," says Rosenberg, "485,000 Americans die of cancer. We desperately need new treatments. One dream has been to harness the body's own defense mechanisms. It has turned out to be an extraordinarily difficult and challenging job." And it will not be finished for some time.

With reporting by J. Madeleine Nash/Chicago