Tuesday, June 5, 2018

Immunotherapy: Medicine’s Most Exciting Frontier: By LAWRENCE GALTON

Courtesy Readers Digest 1981. November.
From the frontiers of science and the far horizons of personal courage, these stories of medical triumphs and miracles will reaffirm your faith in the awesome powers of the human spirit. Dramatic victories and human triumphs
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 immune activities.  Today, many cancer scientists are aggressively pursuing the idea that if one could remove this “blocking factor,” the cancer patient should be able to attack his disease more effectively with his own immune cells.  Until recently, no one has been able to devise a way to put the theory to the real test.  For the only way to remove the blocking factor is to exchange all to the patient’s blood daily with normal blood—a so-called exchange transfusion.  Such an experiment was considered impossible, since it would require not only several thousand pints of blood, but also the simultaneous presence in one cancer center of facilities, equipment and skills rarely available in one place.
In the winter of 1974, however, the beginnings of the crucial experiment were set in motion at the Mercy Catholic Medical Center in Philadelphia be Dr. Isaac Djerassi, who pioneered platelet transfusion to stop incontrollable bleeding in cancer patients.  Dr. Djerassi selected a volunteer with malignant melanoma for who no other useful treatment was available.  The patient, though in good general condition, had a tumor, which could be easily inspected, touched and measured, so that any change could be readily detected.
Plastic tubes were placed in the patient’s wrist artery and vein, and attached daily to a machine, which continuously separated the blood cells from the fluid part of the blood—the plasma that may contain the blocking antibodies.  While the machine returned the blood cells to the patient, Dr. Djerassi kept out the plasma and it its place injected normal plasma back into the patient.  In this fashion, Djerassi exchanged all of the patient’s blood plasma twice daily, using the plasma from 30 to 40 pints of blood everyday.
Dr. Djerassi turned to leading cancer scientists for help in evaluating the results of the experiment.  Regular simultaneous telephone conferences were held, and decisions were made jointly as to what studies to make and who would make then.  Appropriate blood specimens were collected from the patient and dispatched to the other investigators.  All results were reported during the next telephone conference.
Eighteen days after the beginning of the daily exchange transfusions, the patient’s tumor was measurably smaller.  Though the doctors could not halt the tumor growth completely [once the transfusions were stopped the growth began again], they have made much progress in researching the vital questions about what caused their temporary success.
The remissive effect on the tumor seems to have been due to the removal of the blocking factor from the patient’s blood, and possibly, because in the normal plasma given in the patient, there was some crucial component which the patient did not possess.  Additional work with many patients is needed before the final answers will be forthcoming, but Dr. Djerassi feels that the cancer scientists are on the right track in pursuing this line of research.
Despite the abundance of promise in immunotherapy, researchers are proceeding cautiously, wary of missteps, aware that much remains to be learned about how to manipulate most effectively and safely what is probably the body’s most complex and fundamental system.  But distinguished immunologist and Sasker Award winner has observed: “Recent developments are asking up to nothing less than an entirely new picture of how the immune system works.  It is as though we had been viewing things out of focus for years, and now suddenly, they have become sharply defined”.
“In immunology,” says immunology authority Sir McFarland Burnet, “we are part of the wave of the future.”  With that, few would disagree.

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