The announcement last week that white blood cells could be turned into cancer killers captured headlines across America and the hopes of thousands of patients that a cure is here.
But a new era in cancer treatment may be at hand. Since the turn of the century, scientists have struggled to find ways to boost the patient's own immune system to destroy cancer cells. The research has produced tantalizing results with a few dramatic cures, but no consistent successes.
The latest excitement comes from the National Cancer Institute, where researchers led by surgery chief Dr. Steven A. Rosenberg have taken white blood cells from the bodies of patients and treated the cells with interleukin-2 (IL-2), a hormone that turns them into lymphokine-activated killer (LAK) cells. These LAK cells can be injected back into the patient's bloodstream, where they appear to destroy cancers of the lung, colon, rectum, kidney and skin while sparing normal cells.
Preliminary results of the NCI study were rushed into print by The New England Journal of Medicine last week, putting the stamp of approval of the country's most influential medical journal on work by the nation's leading cancer research organization.
The NCI work is the latest advance in an emerging field called biological response modifiers (BRMs), which may provide the first wholly new approach to cancer treatment since nitrogen mustard was first used as a form of chemotherapy more than four decades ago. Currently, the main treatments for cancer are surgery, radiation therapy and chemotherapy.
Early work in the new biological approaches "have been going on since the last century," says Dr. Dan Longo, director of the NCI's biological response modifiers program. "But a scientific approach has only been possible since the application of gene cloning techniques."
By using gene engineering and other techniques, scientists have been able to produce bucketfuls of previously scarce, naturally occurring hormones such as interferon, interleukin-2, tumor necrosis factor and monoclonal antibodies.
All of these BRM compounds exploit some fundamental biological difference between cancer cells and normal cells so they can be identified and selectively destroyed.
BRMs fall into three basic categories, says Longo:
*Chemicals that improve the immune system's response, such as IL-2.
*Chemicals that directly inhibit the cancer cells' growth, such as interferon and tumor necrosis factor, or cells that directly attack the cancer, such as the IL-2-stimulated LAK cells.
*Biological approaches to hindering cancer cells, such as a technique developed by NCI's Dr. Lance Liotta that prevents the spread of tumor cells by blocking a specific protein on the cancer cell's surface.
Other BRM agents include crude preparations that seem to make cancer cells revert to normal cells; chemicals that block tumor growth hormones; and chemicals to block tumor angiogenesis factor, a hormone that makes blood vessels grow into the tumor to nourish it. Researchers are also looking for chemicals that will turn off the very cancer genes -- called oncogenes -- that turn a normal cell into a cancer cell.
The field also includes monoclonal antibody technology. Antibodies are immune system proteins that protect against foreign organisms. Monoclonal antibodies can be used against the cancer directly or to concentrate poisons or radioactive particles on the cancer cells.
This is cutting edge research. None of the BRM agents will be available for routine treatment of cancer for years, maybe decades. Interferon still is only available in a few research centers, and IL-2 won't be available even to research centers for another year or so.
Interferon, a regulating hormone of the immune system, was the first widely publicized BRM. In the late 1970s, it was heralded as a cancer panacea. It wasn't, but it did produce some very good results in a few types of cancer.
In 1979, Dr. Jordan Gutterman, chief of biological therapy at the University of Texas' M.D. Anderson Hospital and Tumor Institute in Houston, reported that partially pure interferon shrank the cancers of 13 of 38 patients by more than half and three patients appeared to be disease-free.
For a year, headlines heralded the wonders of interferon. Biotechnology, using the newest genetic engineering techniques, cloned genes for the different types of interferon and made the once-scarce hormone widely available for tests in hundreds of patients. As more patients were studied, it became clear that interferon was not a magic bullet. Six years later, all 38 of the original interferon-treated patients -- who were seriously ill when treatment began -- are dead.
Gene engineering now produces gallons of another scarce immune system hormone: interleukin-2. Discovered in 1976 by an NCI team led by Dr. Robert Gallo, best known for his role in discovering the virus that causes acquired immune deficiency syndrome, IL-2 is able to activate specialized white blood cells that appear to directly attack and kill cancer cells.
Rosenberg's report of the preliminary IL-2 and LAK cell results, however, sound hauntingly familiar to the first interferon reports. Twenty-five patients have been studied for a short period of time. Of the 25, the cancers measurably shrank by more than half in 11 patients and completely disappeared in only one.
The study "has dealt only with patients in whom nothing else, no drug, no surgery, no radiation, would be expected to produce any response," NCI's Longo says. "In that kind of a setting, seeing 50 percent of a regression feels like an enormous victory."
Whether or not these positive results will continue as other research centers begin testing the procedure is unknown. Significant questions remain about how the treatment works, how much should be given and when should it be stopped. It's also unclear how long the effects last. The patients have been followed for short periods of time, 10 months at the longest. Cancer cures typically are measured in years, usually five.
It may turn out that IL-2 alone will not be enough, just as interferon alone was not enough.
The immune system produces a cascade of regulating chemicals, says Dr. Lloyd Old of Memorial Sloan-Kettering Cancer Center in New York. Many of them may be needed together to produce a cancer-killing effect.
"It may help us understand why interferon has been disappointing in clinical trials," says Old. "The body does not produce interferon alone. It produces interferon, interleukin-1 and interleukin-2 and tumor necrosis factor and antibodies. All are part of the same response."
Despite the unanswered questions, "Steve Rosenberg's finding is not only very exciting but very important," says Dr. Frank Rauscher Jr., vice president for research of the American Cancer Society. "We have long known that cancer treatment fails with surgery and radiotherapy . . . because up to 60 percent [of cancers have spread throughout the body] by the time the patient sees the doctor. Rosenberg and others have provided another systemic treatment. That will not only get at all the primary [cancer], but at metastatic lesions [the tumor cells which have spread to other parts of the body], which is why most patients die."
"To a certain extent, we have plateaued in the ability to manage systemic disease with chemotherapy," says Dr. John Potter, director of the Vincent T. Lombardi Cancer Research Center at Georgetown University. "There have been dramatic advances in the last 20 years in testicular and leumkemia, but not as good a result in lung cancer, colon cancer and pancreas cancer once it has spread.
"Dr. Rosenberg's discovery is exciting, novel, and has shown encouraging preliminary results. Where this will settle out, in the long range, remains to be determined."