Humans are under constant siege by these voracious adversaries. Germs of every description strive tirelessly to invade the comfortably warm and bountiful body, entering through the skin or by way of the eyes, nose, ears and mouth.. Fortunately for man's survival, most of them fail in their assault. They are repelled by the tough barrier of the skin, overcome by the natural pesticides in sweat, saliva and tears, dissolved by stomach acids or trapped in the sticky mucus of the nose or throat before being expelled by a sneeze or a cough. But the organisms are extraordinarily persistent, and some occasionally breach the outer defenses. After entering the bloodstream and tissues, they multiply at an alarming rate and begin destroying vital body cells.
The invaders soon receive a rude shock, for they encounter one of nature's most incredible and complex creations: the human immune system. Inside the body, a trillion highly specialized cells, regulated by dozens of remarkable proteins and honed by hundreds of millions of years of evolution, launch an unending battle against the alien organisms. It is high-pitched biological warfare, orchestrated with such skill and precision that illness in the average human being is relatively rare.
Early warning cells constantly monitor the bloodstream and tissues for signs of the enemy. With the gusto of Pac-Man, they gobble up anything that is foreign to the body. They envelop dust particles, pollutants, microorganisms and even the debris of battle: remnants of invaders and infected or damaged body cells. Other early warners direct the production of unique killer cells, each designed to attack and destroy a particular type of intruder. Some of the killers, alerted to body cells
Painful shot: two-month-old Austin Reed is inoculated with an experimental vaccine against meningitis that have become cancerous, may annihilate these too. Endowed with such specialized weapons, the properly functioning immune system is a formidable barrier to disease. Even when an infection is severe enough to overcome the system's initial response and cause illness, the immune cells are usually able to regroup, call up reinforcements and eventually rout the invaders. But when the system is weakened by previous illness or advancing age, for example, the body becomes more vulnerable to cancers and a host of infectious diseases. And should the system overreact or go awry, it can cause troublesome allergies and serious disorders called autoimmune diseases. As they probe the intricate workings of the immune system, scientists are awestruck. It is an enormous edifice, like a cathedral, says Nobel Laureate Baruj Benacerraf, president of
Knowledge about the inner workings of the immune system has undergone an astonishing explosion in the past five years. Although researchers began to pry loose its secrets in the late 19th century, it was not until after World War 11 that the pace of discovery began to quicken, boosted by such achievements as the deciphering of the genetic code and recombinant DNA technology. But no early advances can match those of recent years, which have enabled doctors to devise - ingenious new treatments for a host of disorders. Says Immunologist John Kappler, of the National Jewish Center for Immunology and Respiratory Medicine in
Kappler is not exaggerating. In the past few months alone, dozens of new immune discoveries and promising therapies have been reported. Researchers announced in March that by activating certain immune cells, they had increased by 20% the five-year survival rate of patients in the early stages of lung cancer. In the same month, European scientists reported eliminating the need for insulin shots in some diabetic children by administering a drug that suppresses the immune system. Researchers in
Now, however, scientists have a good grasp not only of the broad workings of the immune system but of many of the nittygritty details as well. In a typical infection, for example, a flu virus burrows into a cell in the lining of an air passage, takes over the machinery of the cell, and orders it to produce more flu viruses. Quickly engorged, the invaded cell bursts, releasing new viruses to infiltrate other cells and replicate further. Left unchecked, the onslaught would eventually kill enough cells to cause death. But the intruders soon encounter roving scavenger cells called phagocytes, which simply engulf and digest them. These defenders-monocytes, neutrophils and macrophages-secrete substances that dilate nearby blood vessels and make them more permeable, enabling even more defenders to get from the bloodstream to the infection site. Other proteins, those belonging to the complement system, aid in this process.
Upon meeting a virus, the macrophage, which moves about, amoeba-like, on long cellular extensions known as pseudopods (false feet), does more than just ingest the intruder. It has another, even more important function. On its surface, like virtuatly all body cells, the macrophage carries MHC (for major histocompatibility complex) molecules, protein badges that enable other immune cells to recognize the macrophage as friend, or self, and not attack it. After digesting the virus, the macrophage proudly displays strips of protein from the virus in the grooves of some of its MHC molecules. Once a bit of protein which is part of the virus's own identity molecule, or antigen-is nestled in the groove of the macrophage's MHC molecule, it acts as a red flag for the immune system, warning it that a particular type of virus is loose in the body.
At this point, it's still a race between the immune system and the virus, says Dr.Carl Nathan of
The rapidly multiplying helper T cells now begin releasing a flood of their own chemical signals, the so-called lymphokines, which include gamma interferon and other types of interleukin. These stimulate the defense system even more, spurring the proliferation of phagocytes, including macrophages, and other immune fighters something like a draft call in wartime. The result is the familiar swelling and inflammation of an infection.
At the same time, other helper T cells in the lymph nodes move to couple with yet another kind of immune fighter, the B cells. Releasing still more chemicals, the helper T cells stimulate the B cells to reproduce. These proliferating B cells then mature into plasma cells, which DNAX's Coffman calls dedicated antibody factories, that begin to mass-produce antibodies. Antibodies are proteins capable of recognizing and binding specifically to the flu virus that triggered the alarm. Circulating in the blood to seek out their quarry, they begin attaching themselves to the viruses, signaling the macrophages and other immune scavengers to move in for the kill.
Meanwhile, gamma interferon released by the T cells has not only slowed viral replication but also whipped the macrophages into a feeding fury. Their cell membranes become ruffled, their feet more numerous and their appetites ferocious. They don't necessarily eat faster, notes Dr. Richard Johnston Jr. of the University of Pennsylvania School of Medicine, but they kill better.
The flu viruses, however, are not finished yet. Those still multiplying inside the body's cells are momentarily safe from scavengers and antibodies, but the free lunch is over quickly. While the B cells are being activated, other helper T cells have been creating an army of killer T cells. These killers recognize the flu-ridden cells because, like macrophages, infected cells display a bit of viral antigen on their outer membranes. Says Coffman: For many viral infections, the most important response is the killer T cell. Viruses live inside cells, so it's essential to kill not only the viruses themselves but those cells that are infected with the virus
The killer T cells are relentless. Docking with infected cells, they shoot lethal proteins at the cell membrane. Holes form where the protein molecules hit, and the cell, dying, leaks out its insides. To ensure that the cell and its viral occupants are destroyed, the killer T cells then deliver the coup de grace by transmitting a signal that causes the cell to chew up DNA from both itself and the virus. Explains Dr. Irving Weissman of Stanford: This is an overlapping, dual system of killing that ensures that the seed of viral production will be eliminated from the body.
When victory over the virus is achieved, the wildly accelerating responses of the immune system slow, then shut down. Scientists believe that still other immune specialists, known as suppressor T cells, call off the battle. As the carnage wanes, the B cells and T cells perform a last, vastly important task: they form memory cells that circulate in the bloodstream and lymph system for many years, primed to spring into action should the same strain of flu virus ever attack again. In addition, the body is protected by specialized antibodies, strategically deployed in mucus, saliva and tears, that immediately recognize any return of this particular virus.
While a healthy immune system may take as long as three weeks to complete the job against a specific flu virus, its next response to the same viral strain reaches full force immediately, and the invaders are overcome before they can do any significant damage. In other words, the body has become immune-but only to that specific virus. You probably wouldn't even know you'd been reinfected, says Carl Nathan. The immune system has a short track and a long track, and it all depends on whether it's a first encounter or you've seen it before.
How did this astonishing biochemical system develop? The first stages in its evolution are a mystery. But scientists have deduced from the study of primitive species that rudimentary mechanisms against infection existed in various forms of life more than a billion years ago. The first inkling of such progenitors came in 1883, when Russian Zoologist Elie Metchnikoff stuck a rose thorn into the larva of a starfish and a short time later observed that the thorn had been completely surrounded by cells. The cells were phagocytes. These little guys go back in evolution a very long way, says Carol Reinisch of the Tufts School of Veterinary Medicine. They have the ability to distinguish between self and nonself, which is the crucial distinction.
Over the eons, these primitive defenders developed increasingly sophisticated weapons to fight off microorganisms, which could mutate far more rapidly and thus evolve faster than higher forms of life. But it was probably not until about 600 million years ago, about the time vertebrates began to emerge, that the modern immune system, with its T cells and B cells, began to take shape. Once in place, these two cell types must have quickly evened the odds, since they have the remarkable ability of producing, respectively, a staggering variety of killer T cells and antibodies capable of attacking any invader.
How these immune cells produce such diversity was elucidated during the mid-1970s by Immunologist Susumu Tonegawa, now at M.I.T., who in 1987 was awarded the Nobel Prize for his achievement. Tonegawa proved that the B-cell genes that dictate the production of antibodies occur in distinct segments. These pieces, like cards in the hands of a
Long before scientists even began to unravel the mysteries of this remarkable system, the ancients were aware of immunity. They knew from experience that anyone who survived certain diseases would not be likely to get them again. As early as the IIth century, Chinese doctors were manipulating the immune system. By blowing pulverized scabs from a smallpox victim into their patients' nostrils, they could often induce a mild case of the disease that prevented a more severe onslaught. In the 1700s, people rubbed their skin with dried scabs to protect themselves against the disease.
These primitive practices were introduced to
In 1880 Louis Pasteur, a French microbiologist, concocted a vaccine against chicken cholera after discovering that weakened cholera organisms, while incapable of making chickens sick, would immunize them against the malady. Pasteur, who is credited with founding the science of immunology, went on to create a human rabies vaccine from the brains of rabies-infected sheep and rabbits
Building on Pasteur's work, 20th century scientists have learned to mass-produce bacteria and viruses, then weaken or kill them and use them as the major ingredient in vaccines for such varied diseases as typhus, yellow fever, influenza, polio, measles and rubella. Unfortunately, the vaccines occasionally cause the disease they are designed to ward off. (Reason: the killed viruses sometimes survive, while the weakened versions often fail to cause an immune response.) In general, however, the vaccines have been quite effective; in recent years the National Academy of Sciences has reported only a handful of polio and diphtheria cases and only a few deaths caused by whooping cough and rubella. Maurice Hillemen, director of
These days the explosive growth of both molecular biology and immunology has enabled vaccine makers to take a safer and more effective approach to their work. Instead of using dead or attenuated bacteria or viruses, they remove from the bug's surface the marker protein, or antigen, that provokes the immune response. Employing gene-splicing techniques, they mass-produce the antigen, or a portion of it, and use it as the prime ingredient of the vaccine.
Researchers are also creating vaccines that consist largely of antigens synthesized from chemicals on the laboratory shelf When these vaccines prove ineffective, scientists can now usually determine why. Says M.I.T. Molecular Biologist Malcolm Gefter: Today, when a vaccine doesn't elicit a protective response, it is possible to detect what is or is not working-the B cells, the T cells, the lymphokines, whatever. Scientists can then fix the vaccine. For example, the 1985 vaccine against Hemophilus influenzae Type B, which causes bacterial meningitis, was only partially effective; although it protected older children, it did not work for babies under two years, who are most at risk. The antigen used to make the original vaccine has been re-engineered to make it more potent, and the new vaccine is being tested in infants.
Despite such advanced techniques, it seems tougher than ever to create new vaccines. Some viruses, bacteria and parasites are so complex and well evolved in their defenses against an immune reaction that no vaccine strategy has yet been entirely effective. Flu viruses, for example, mutate rapidly, continually changing their antigens in the process. As a result, an immune system strengthened by a flu shot against last year's predominant strain of flu will probably not be helped by it this year. The common cold virus is also troublesome, because it comes in at least 100 identifiable varieties. The parasite that causes malaria poses still other problems: it penetrates cells so quickly that it is hidden from antibodies. To complicate matters, it goes through three stages of life, displaying different antigens in each stage. Because none of the malaria vaccines yet developed can cope with these diverse strategies, the affliction is still rampant in the tropics.
Such challenges to the vaccine makers, however, pale in comparison with that presented by the AIDS virus. Says M.I.T's Gefter: We're looking at a strong, well devolved, well-designed organism that is doing whatever it can to protect itself. The AIDS virus mutates twice as fast as the flu bug. It can lie dormant in body cells, where antibodies cannot attack it, without revealing its telltale antigen (a dead giveaway to killer cells). New findings indicate that the virus also uses immunological decoys that provoke impotent immune responses. Worst of all, the AIDS virus is unique in that it can mount a speedy and lethal attack on helper T cells, which cripples the immune system before it can counterattack. This means that to prevent an AIDS infection from taking hold, a vaccine must stimulate the immune system to incapacitate the AIDS virus immediately after exposure, before it can penetrate the helper T cells.
Scientists are scrutinizing the AIDS virus for any sections of its outer coat that remain unchanged during its rapid mutations. With antigens from these sections, they hope to produce a vaccine that will remain effective despite many mutations. A group led by Dr. Daniel Zagury at the
Even without provocation by the AIDS virus or other infectious organisms, the immune system can sometimes go awry. Often, entirely on its own, it can over respond, fail to respond or turn against the body it is designed to protect with the same lethal fury it directs against invaders and cancerous cells. Some 80 immune system deficiencies have been identified so far. About one in 400 people has at least one immune-system component missing or malfunctioning, usually for genetic reasons. In one in 10,000 people, the deficiency leads to serious disorders. Perhaps the most tragic example is severe combined immunodeficiency disease, a rare condition in which both B cells and T cells are lacking. The most famous SCID victim, a
As hay fever and other allergy sufferers will testify, the immune system can sometimes react to pollen, animal dander,molds and drugs that are normally harmless. In allergy victims, however, the immune system goes into high gear at the appearance of these substances, or allergens. It begins producing antibodies called immunoglobulin E, which attach themselves to mast cells located in the tissues of the skin, in the linings of the respiratory and intestinal tracts, and around the blood vessels. The mast cells promptly begin to release a number of chemical signals, including histamine, a substance that dilates blood vessels and makes it easier for cells to pass through the capillary walls.
These changes, meant to expedite the arrival of immune cells, cause the inflammation and swelling associated with allergic reactions. Allergy sufferers are now treated with antihistamines, which temporarily block the immune response, as well as steroid nasal sprays and inhalers, which reduce inflammation. But more effective help may be on the way. Scientists have synthesized bits of protein molecules that prevent immunoglobulin E antibodies from setting off an allergic reaction.
One of the more devastating errors of the immune system involves its failure to distinguish between self and nonself, resulting in so-called autoimmune diseases, which can be crippling and sometimes fatal. Dozens of disorders that once mystified doctors are now thought to be autoimmune. Among them: Type I diabetes,myasthenia gravis, multiple sclerosis rheumatoid arthritis and systemic lupus. erythernatosus. In these and other autoimmune diseases, the immune system mounts a selective and ferocious assault against parts of the body, destroying cells or cell components that it mistakenly identifies as alien.
Type I diabetes, for example, which afflicts 1.5 million Americans and is brought on by an insufficient supply of insulin, was for years believed to be caused by a virus. Researchers have now shown that it probably results from a defective immune system. For reasons that are not yet clear, immune cells invade the pancreas and destroy the beta cells, which produce insulin. When this happens, the body cannot convert sugar into the energy that cells need to function. The cells starve, and the unconverted sugar builds up in the bloodstream, damaging the fragile lining of blood vessels. Complications associated with Type I diabetes include heart and kidney disease, poor circulation, eye problems and stroke.
However incomplete, the emerging understanding of the immune system's role in Type I diabetes has le to an experimental treatment. In Canada and Europe, researchers have weaned diabetics from their insulin shots after giving them cyclosporine, a drug used in organ transplants to suppress the immune system. Doses of cyclosporine, which works by dampening T-cell attacks on the beta cells, have provided dramatic results: many patients have been able to discontinue their insulin shots for up to a year. Still, by undermining the entire immune system, cyclosporine leaves the diabetic more vulnerable to other diseases. And when given in high doses, it can have serious side effects, including kidney damage.
In an attempt to find a more selective treatment for Type I diabetes, researchers are trying to figure out exactly why the immune system attacks the beta cells. Last October a Stanford University team discovered errant forms of a gene that controls the development and growth of the culprit T cells. The team's conjecture: in Type I diabetics, this gene produces a protein badge that differs slightly from the norm in structure, causing the immune system to attack the beta cells. Eventually, the group hopes to find a way to neutralize the harmful effects of the molecule and thus eliminate the need for immune suppressants like cyclosporine.
Another autoimmune disease, myasthenia gravis, a neuromuscular disorder that afflicts 15,000 Americans, is caused by antibodies that attack vital links in the nervous system, and leads to gradual loss of muscular control. Initial studies suggest that small doses of cyclosporine may be effective in blunting the symptoms of the disease. Some researchers, however, are searching for a more selective remedy that involves mass-producing antibodies that are specific to one antigen. These so called monoclonal antibodies are designed to immobilize only those B cells that produce the antibodies responsible for the disease.
Some of the most promising new therapies arising from recent research involve the chemical signals, or lymphokines, that regulate the immune system. These extraordinary proteins have a bewildering array of names and functions. There are, for instance, three types of interferon-alpha, beta and gamma. Alpha alone comes in more than a dozen varieties. Interleukins are similarly prolific. We are already up to interleukin-7 and interteukin-8, says Immunologist Lloyd Old, of the Memorial Sloan-Kettering Cancer Center in Manhattan, and one can expect that we will go on from there. Scientists have so far discovered at least five different colony-stimulating factors, which cause cells in the bone marrow to mature and differentiate into red and white blood cells. Each of the players seems to have a vital, if sometimes overlapping, role.
Using bioengineering techniques, medical researchers have begun to mass-produce these substances and use them, sometimes in combined cocktails, to boost the immune system against specific diseases. In clinical trials at Boston's New England Deaconess Hospital, Dr. Jerome Groopman has found that granulocyte-macrophage colony-stimulating factor reverses bone marrow failure and boosts white-cell counts in AIDS patients. Gamma interferon seems to remedy the defective functioning of monocytes and macrophages in a wide variety of diseases. Alpha interferon has been particularly effective against two types of leukemia and non-Hodgkin's lymphoma, a cancer of the lymph system. Says Dr. Jordan Gutterman, of Houston's M.D. Anderson Hospital and Tumor Institute: There are ten different tumors in which potentially important anti tumor activity by interferon has been demonstrated.
Interleukin-2 has shown promising results in treating advanced skin and kidney cancers. In fact, says Gutterman, there appears to be tremendous synergy between alpha interferon and IL-2 in attacking cancer cells. While IL-2 works to make the killer cells more potent, he explains, they have to recognize something unique on the surface of the cancer cell in order to kill it. That something is an antigen, and interferon seems to make it more visible to the killer cells.
Scientists are proceeding cautiously with the new therapies. In any substance that is immunologically active, observes Genentech's Sherwin, you run the risk of tilting the balance in an unfavorable way. We don't know all of the answers yet. That may be an understatement. Immunologist Leroy Hood of the California Institute of Technology is certain that the lymphokines discovered so far are just the tip of the iceberg and that more subcategories of T cells will be found, He emphasizes that scientists do not yet fully understand, among other things, how B and T cells differentiate, and how the immune system's genes are turned on and off at different times. In the truest sense, he says, immunology is just in its youth. Still, says Sherwin, there's an enormous amount we know now that we didn't know five years ago, and five years from now we'll know even more. Immunology may indeed still be in its youth, but it is
growing up fast.
THE BODY ‘S DEFENSES
Some of the immune system's biggest battles are directed not against harmful intruders but against potentially lifesaving organ transplants. New hearts and kidneys in adults have become fairly commonplace, and top surgeons have even attempted the daunting feat of transplanting multiple abdominal organs into infants and toddlers. Today's organ recipients are indebted to a drug called cyclosporine, which has revolutionized transplantation technology in the past decade. Unlike immunological treatments for AII)s and cancer, cyclosporine works by temporarily suppressing the body's natural defenses, thus preventing the rejection of grafted tissue.
The miracle of cyclosporine comes at a steep price. The drug can cause severe damage to the kidneys as well as allow cancerous tumors to develop. Moreover, cyclosporine costs as much as $6,000 for a year's supply, and patients may need it for life. Still, declares Calvin Stiller, chief of transplantation at University Hospital in London, Ont., cyclosporine clearly stands out as the most important medical discovery in transplantation. It changed the field.
Ever since the pioneering transplant the 1960s, the chief obstacle to the full recovery of transplant patients has been the immune system's xenophobic zeal to destroy anything that is foreign to the body. Once the alien threat has been identified, agents known as helper T cells unleash the powerful immune response that attacks grafted tissue. During the 1970s, physicians found that they could minimize this reaction by more closely matching the MHC proteins, or immunological dog tags, of a donor with those of the recipient. Even so, they could not completely eliminate the rejection response. To make matters worse, the only drugs available to weaken it shut down the defensive system completely, leaving patients vulnerable to viruses, bacteria or tumors. The triple threat of rejection, infection and malignancy kept transplant surgery to a minimum. Enter cyclosporine. Discovered in 1970 by a scientist at Sandoz, a Swiss pharmaceutical company, the drug was nearly abandoned as worthless. Unexpectedly, however, researchers found that it was a highly selective suppressor of helper T cells. By preventing the activation of the T cells, the drug interferes with the body's instinct to attack a transplanted organ. Yet unlike other suppressants, it does not affect other parts of the immune system. Cyclosporine is thus able to dampen the rejection reaction while leaving a large part of the body's infection-fighting defenses intact.
Physicians began testing the drug on humans in 1978. The results were dramatic. Both rejection and infection continued to be problems, but survival rates one year after transplantation rose from 32% to 70% for liver patients and from 54% to 77% for kidney patients. By early 1980, recalls Thomas Starzl of the University of Pittsburgh, a leading transplant surgeon, we had a sense that there was a tremendous change in outlook in both kidneys and livers, and that enthusiasm quickly spread to the heart. Cyclosporine is highly toxic, however, and researchers have begun to look for alternatives. Ideally, they foresee a therapy that would prevent rejection but also persuade the immune system to tolerate a transplanted organ even after treatment is halted.
For now, surgeons and their patients must still walk the tightrope between the natural potency of the immune system and the perils of suppressing it. The balancing act is especially tricky in the most difficult of operations: multiple abdominal transplants. Doctors in the U.S. have tried such surgery only four times in the past four years. Just one patient, now seriously ill, survives. Tenmonth-old Michael Steward of Chicago received a new liver, pancreas, small intestine and part of the stomach in February to correct a congenital defect. Last week, a record 6 1/2 months after a similar operation, three year old Tabatha Foster of Madisonville,Ky., succumbed to cancer. The lesson: physicians have a great deal more to learn before they can manipulate the immune system at will.
THERAPIES BOLSTER AGAINST CANCER
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 more $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 42 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.
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