Immunotherapy: Medicine’s Most Exciting Frontier
By LAWRENCE GALTON
Of all fields of medical research, none is so full of promise as immunotherapy—the manipulation of the body’s natural defense system to make it fight off diseases, which have previously overwhelmed it.
Consider the California boy who suffered recurrent episodes of infection, including several bouts pneumonia, abnormal bleeding, an enlarged spleen and loss of hair. He was born with an immune system so impaired that it offered no defense against certain disease organisms. After injections of a substance called “transfer factor”’ every six months, the boy was kept free of infection for 48 months. Extracted from the Shiite blood cells of healthy individuals, transfer factor is capable of temporarily transferring specific immunes response from on person to the faulty immune system of another.
By a similar manipulation, an eight-year old Florida girl whose body for years was encrusted with disfiguring sores caused by a chronic fungus infection has became a clear skinned child.
An estimated ten million Americans have diseases for which immunotherapy bay be of use. The diseases include cancers, arthritis, rheumatic heart disease, certain kidney ailments, a number of infectious diseases and multiple sclerosis. In addition, many of the millions who suffer from allergies may ultimately benefit.
Once thought to be involved only in defense against infection, the immune system is now known to be considered with recognizing and combating all types of foreign materials that threaten the body’s integrity, including cancer cells, which probably develop many times throughout life. There are at least two types of lymphocytes [a variety of site blood cells] those that act by themselves ad those that synthesize antibodies. They make up the two major combative forces of the immune system. The first type of lymphocyte can learn to recognize disease organisms and other foreign materials and, once having learned, can remember and react to the any time they reappear. Among other reactions, these lymphocytes can release substances, which direct big scavenger cells—macrophages—to attack enemies. Usually, it takes 4 to 48 hours for a lymphocyte corps to congregate at an intrusion site.
Meanwhile, the second force, the antibodies—protein molecules known as immunoglobulins—may attack. The immune system turns out specific antibodies to fit specific antigens [foreign materials that provoke immune forces] almost the way a key fits a lock, and the fit inactivates the antigen. Antibodies circulate in the blood and can act within five seconds; some need help from a complex group of substances in the blood called “complement” which can split apart invading bacteria, viruses and other foreign materials.
One immunologic manipulation—vaccination—has been used since Dr.Edward Jenner discovered it as a weapon against smallpox in 1796. In recent years, attempts to transplant kidneys and other organs have given tremendous impetus to further study of other manipulations. Early on, the body—attacked and sloughed off because their foreignness aroused and the immune system quickly rejected transplanted organs. Powerful drugs, employed in anticancer therapy, were used to suppress the immune system, but then patients were left wide open to deadly infections.
The phenomenon noted among early transplant patients was that suppression of the immune system made them more prone to certain types of cancer. Did immune system play a role in preventing cancer? In 1950s, it was discovered that the surfaces of cancer cells contained antigens not present on normal cells, and that these could arouse the immune system. Doon, a surveillance theory, which is still debated, was developed; normal body cells are always, in small numbers, turning malignant, and a major job of the immune system is to search them out and destroy them.
Some years ago, DR. Edmund Klein, chief of dermatology at Roswell Park Memorial Institute, Buffalo, New York, began studies testing cytotoxic drugs [drugs that kill cells] on skin tumors. Some to these chemicals combined with tissue materials, resulting in highly antigenic compounds that aroused the patient’s immune system, causing it to attack the tumor. An agry red reaction occurred at the site, and before long the tumor disappeared as normal tissue grew in to resurface the area where tumor had been. Here was the first clear evidence that the immune system could destroy a cancer. Later, Klein and his team of researchers went on to show that separated components called ‘lymphokines’ [which are produced by a group of white blood cells] could bring about similar reactions against tumor.
Over the years, Dr. Klein found that, at least in skin cancers, immunotherapy could eradicate lesions in more than 70% of patients, with no recurrences for up to 15 years. New skin tumors, however, did occur, but at a greatly diminished rate. Klein and his co-workers found that immunotherapy could ferret out and eliminate skin cells not yet malignant but on they’re way to becoming so. When the oblivious skin cancers were treated, a dozen or more other tiny areas, previously unnoticeable, reacted. They proved to be pre-malignant or in very early stages of malignancy. “We found,” says Klein, “that the immune system was a lot smarter than we were and could combat tumors we didn’t even know existed.”
From researchers around the country and abroad come other reports that science is taking its first uncertain steps on the route to immunotherapy for cancer. In the early 1970s and M.D. Anderson Hospital and Tumor Institute in Houston, for example, Dr Evan M. Hersh and colleagues have used BCG, the tuberculosis vaccine, to treat 300 patients with malignant melanoma [a kind of skin cancer]. Some had had surgery before treatment and were disease-free. In these patients, the BCG clearly prolonged the disease-free interval, compared to controls. In others, who could not be treated surgically because their cancer had spread, chemotherapy plus BCG, compared with the results of chemotherapy alone, prolonged the remission and length of survival.
At a 1972 National Institutes of Health conference on immunotherapy, Dr Sol Roy Rosenthal and other investigators from the University of Illinois reported on a Chicago study: from 1964 through 1969, only one death from leukemia was recorded among 54,414 children up to six years of age who had been vaccinated at birth with BCG against tuberculosis. In contrast, 21 deaths from leukemia were reported among 172,986 children of similar age and race who had not been vaccinated—a rare more than six times as great. A controlled stud has now been set up nationwide by the Children’s Cancer Study Group to investigate BCG as a vaccine against leukemia.
Few investigators believe that the chemicals they are using experimentally today will be the ones in use five years hence, to that immunotherapy alone can be expected to conquer a cancer that has become well established. They see the immunolic killing of such tumor cells as a kind of “numbers game.” Each immune agent has a certain limited capacity to stimulate the immune system. So, when a cancer is well established immunotherapy may be the most effective after the tumor load has been lightened by surgical removal of the primary tumor, or after regression has been induced by chemotherapy.
Once the most fundamental discoveries about the immune system are that it sometimes defeats itself by producing a substance that blocks its own