Arming Cancer's Natural Enemies

By Claudia Wallis

For decades the war against cancer has been waged with three often brutal weapons, the so-called cut, burn and poison methods of rooting out tumors: surgery, radiation and chemotherapy. But slowly, in laboratories and medical centers around the world, a fourth approach has been evolving. The idea: rallying the body's own immunological forces to destroy malignant cells. Last week scientists at the National Cancer Institute in Bethesda, Md., revealed some of the most promising results to date in the use of this new category called immunotherapy. In an unusual "special report," published in the New England Journal of Medicine, Dr. Steven Rosenberg and his NCI colleagues described a complex technique that enables doctors to turn some of a patient's own white blood cells into "killer cells" that attack tumors.

The news prompted tabloid headlines proclaiming CANCER BREAKTHROUGH and led desperate patients around the country to deluge the NCI with requests for the new "cure." Such a reaction is clearly premature, warned Rosenberg (who was a spokesman for the team that treated President Reagan's colon cancer). "I am really anxious that this be kept in perspective," he said. "This is a promising first step in a new approach to use the body's own immune system against cancer. It is certainly not a cancer cure in 1985."

The technique was tested on ten different types of cancer in 25 patients, for whom standard treatments had failed. Crucial to the experiment was a potent natural substance called interleukin-2 (IL-2), one of a variety of chemical messengers called lymphokines that help control the activities of the immune system. Studies have shown that IL-2 is capable of transforming certain white blood cells into powerful, anticancer killer cells. Using an elaborate blood-separating apparatus, Rosenberg and his team withdrew white cells from each patient and treated them with IL-2. After incubating for three or four days, the activated cells were injected back into the patient, along with more IL-2, and the "killers" went to work.

The results were impressive for several types of cancer. In eleven of the 25 patients, tumors shrank by 50% or more. Among the patients showing this response were three out of three with kidney cancer and four out of seven with melanoma, a particularly dangerous form of skin cancer that often spreads to the internal organs. In one melanoma patient who previously had widespread tumors, all signs of malignancy disappeared. There was, however, no response at all in 14 of the patients, and the outlook, even for those who have improved, remains uncertain; none has been observed for more than a year.

The NCI report met with a mixture of optimism and caution in the medical community. "A 50% tumor regression is very good," observed Dr. Kurt Stenzel of the Rogosin Institute at New York Hospital, who is also working with IL-2. "But you still want more," he said. "You want it to go away and never come back." Doctors, including Rosenberg, expressed concern about the treatment's side effects. For most of the patients in the NCI experiment, the treatment caused serious fluid retention, with up to 20 lbs. of water accumulating in the lungs, liver, kidneys and elsewhere in the body. As a result, two patients had life-threatening breathing problems that required emergency intervention.

With further research, Rosenberg hopes to find a way around these difficulties and to make the technique less complicated and less costly. At present, the treatment calls for four to five weeks of hospitalization, a squadron of technicians for each patient and specialized lab facilities, all of which add up to a cost of tens of thousands of dollars for a single treatment. "Most hospitals would find it impossible to perform this procedure," he said. "There are a lot of problems to be worked out."

IL-2 is just one of a number of lymphokines and related natural substances showing promise in the immunological treatment of cancer. Interferons, tumor necrosis factor, interleukin-1 and a substance called colony-stimulating factor all play a role in the normal functioning of the immune system and may ultimately find a place in the treatment of cancer. It has been only within the past five years that genetic-engineering technology has made large quantities of these substances available to researchers. Many physicians believe that IL-2, which has also been genetically engineered, will eventually be used together with some of these other substances. "It may be that for each type of cancer, you need a different combination," suggests Dr. Jordan Gutterman, of Houston's M.D. Anderson Hospital and Tumor Institute. IL-2 may also prove useful in combination with standard chemotherapy or as a follow-up to surgery. Stenzel theorized that after such traditional treatments, IL-2 could "gear up the patient's own cells to scavenge any remaining tumor cells."

Last week the NCI cancer hot lines were besieged with thousands of calls from Americans seeking information about IL-2 treatment. "In many cases, these were people who had no other hope," said Judith Stein of the Cancer Information Service. At present, however, the Institute can treat only eight patients a month and is not accepting new patients. Plans are under way to begin testing the new procedure next year at cancer centers around the country. Dr. Frank Rauscher, a former NCI chief who is now a top official at the American Cancer Society, explained that the excitement in medical circles is for the prospects rather than the accomplishments of IL-2 and other immunological approaches. The results reported last week were a promising opening shot on a new part of the cancer battlefield. Says Rauscher: "We didn't see such results in most of the early chemotherapeutic drugs" two decades ago. But cancer experts unanimously emphasize that the new treatment is nowhere close to being a cure. "We have patients; we have responses," said Rosenberg. "But we're not yet where we want to be."

With reporting by Christine Gorman/New York