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Early in this century, patients with cancer would often seek medical attention only in the final stages of their disease, after their tumors had become massive. Surgeons would attempt to remove these tumors to alleviate their patients’ pain. But since sterile operative techniques were in their infancy and the discovery of antibiotics almost half a century away, such surgery often caused massive and frequently fatal infections.
In a few instances, however, tumor remnants of infected patients would disappear, leaving them healthy and doctors puzzled. Today, after decades of research into how the immune system works, scientists have learned that the seemingly miraculous cures resulted from the infections themselves, which set in motion complex immune reactions.

Understanding the relationship between cancer and the immune system-whose purpose is to find and destroy any abnormal cells in an organism among a mass of normal ones-has resulted partly from so-called “experiments of nature.” A few diseases involving immune deficiencies are associated with higher rates of cancer, for example. A person infected with HIV, for instance, is 100 times more likely to develop a malignancy than an uninfected person. Also, organ-transplant recipients treated for a long time with drugs that suppress the immune system, thereby preventing rejection of the new organs, are many times more likely to develop cancer than the rest of the population. In fact, an elegant demonstration of the immune system’s role in protecting against cancer is the fact that tumors occasionally regress when doctors remove immunosuppressing drugs.

Armed with such discoveries as well as modern biotechnology techniques, researchers have begun using several elements of the immune system to systematically destroy tumor cells. (Of course, immunotherapy is only one of a number of innovative ideas in cancer treatment that hold significant promise. The public investment into cancer research since the Nixon administration declared war on cancer in 1971 is finally starting to produce a variety of innovative techniques, such as methods that exploit the genetics of how a cell becomes malignant.) The work, being conducted on both animal models and people with cancers difficult to eliminate by traditional means, has a long way to go but suggests a more effective way of treating many cancers in the future.

The Problem with Recurrent Cancer

The standard methods for eliminating malignant tumors have long been surgery, radiation, and chemotherapy. The underlying crude assumption is that doctors can generally destroy a cancer without losing the patient to the therapy’s toxic effects. Of course, as researchers have developed supportive care such as powerful antibiotics and growth factors-natural body proteins that can be manufactured using genetic-engineering techniques and that cause the white-blood-cell count (which plummets after treatments) to recover more quickly-doctors have been able to administer more intensive chemotherapy. These treatments have played a role in the recent good news that the number of U.S. cancer deaths has finally dropped for several consecutive years. Still, 500,000 U.S. residents annually die of malignancies-a number hard on the heels of the country’s number-one killer, cardiovascular disease.

For everyone who has witnessed cancer firsthand-whether as patient, family member, friend, or medical professional-one of the most worrisome and disheartening aspects is that while today’s therapies can generally eradicate all measurable evidence of disease initially, any remaining cells may proliferate and cause a relapse of cancer. And because the first set of remaining cells has resisted chemotherapy, their offspring have a selective advantage to do the same, leaving the person with a recurrence of cancer that is often widespread and much less easily treated with chemotherapy or other techniques.

A critical need, therefore, is to find and eliminate the few remaining cancer cells left viable after conventional therapy. The immune system’s elegant and complex methods of attacking invaders suggest a variety of ways to assail the remaining bits of malignancies. (Another goal is to discard today’s techniques altogether in favor of an entirely different method. But eliminating treatments that now work better than anything else is not judicious until viable alternatives develop.)

At its simplest level, the immune system discriminates between “self” and “nonself” and destroys the latter. In most responses, the system relies partly on antibodies-proteins with two specialized ends. One end of an antibody binds to the infecting cell or virus while the other end attracts immune cells that engulf and digest the invader. The attack also relies on different immune cells, which, upon contact with foreign cells, secrete compounds that make the offenders’ membranes porous so that their vital contents leak out and the cells eventually die.

With this general understanding of the immune system and knowledge of the early reports of tumor regressions after infection, in the 1960s and ’70s clinicians injected some solid tumors with killed or weakened microbes, such as BCG (bacille Calmette-Gurin, an altered form of tuberculosis) and Cornybacteria (the cause of diphtheria), in the hope that such outside organisms would stimulate an immune response. And indeed they did, sometimes destroying the tumor. Although the results were inconsistent, the work demonstrated that “immunotherapy” might someday have a place in the cancer-fighting armamentarium.

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