At the turn of the last century, German bacteriologist Paul Ehrlich developed the concept of the magic bullet-- a substance that could enter the body and destroy diseased cells, yet spare the healthy ones. The biochemicals and cells of the immune system, with their great specificity for attacking non-self tissue, would be ideal magic bullets. Immunotherapy used immune system components to fight disease--both humoral immunity (antibodies) and cell-mediated immunity (cytokines).

Monoclonal Antibodies Target Immunity

Tapping the specificity of a single B cell, and using its single type, or monoclonal, antibody to target a specific antigen (such as on a cancer or bacterial cell) awaited finding a way to entice the normally shortlived mature B cells into persisting in culture. In 1975, British researchers Cesar Milstein and Georges Kohler devised monoclonal antibody (MAb) technology, an ingenious way to capture the antibody-making capacity of a single B cell.

Milstein and Kohler injected a mouse with red blood cells from a sheep. They then isolated a single B cell from the mouse's spleen, and fused it with a cancerous white blood cell from a mouse. The result was a fused cell, or hybridoma, with a valuable pair of talents: like the B cell, it produces large amounts of a single antibody type; like the cancer cell, it divides continuously.

MAbs are used in basic research, veterinary and human health care, and agriculture. Cell biologists use pure antibodies to localize and isolate proteins. Diagnostic MAb kits detect tiny amounts of a single molecule. Most kits consist of a paper strip impregnated with a MAb, to which the user adds a body fluid. For example, a woman who suspects she is pregnant places drops of her urine onto the paper. A color change ensues if the MAb binds to human chorionic gonadotropin, indicating pregnancy.

MAbs can highlight cancer before it can be detected by other means. The MAb is attached to a radioactive chemical, which is then detected when the MAb binds an antigen unique to the cancer cell surfaces. Detecting a cancer's recurrence with a MAb requires only an injection followed by a painless imaging procedure--compared to surgery.

In cancer treatment, MAbs hold the promise of being magic bullets that ferry conventional cancer treatments to where they are needed and limit their toxicity. Drugs or radioactive chemicals are attached to MAbs that are attracted to antigens on cancer cells. When injected into a patient, the MAb and its cargo are engulfed by the cancer cells, which are destroyed. Because many people have allergic reactions to MAbs derived from mice, geneticists have engineered mice and bacteria to secrete human antibodies.

Cytokines

Immunotherapy experiments were difficult to do in the late 1960s because the needed biochemicals could only be obtained in small amounts from the cadavers. In the 1970s, however, the advent of recombinant DNA and monoclonal antibody technologies provided the ability to make unlimited amounts of pure proteins--just as the first inklings of the AIDS epidemic were making it essential to find a purer source than cadavers!

Interferon was the first cytokine to be tested on a large scale. Although interferon did not live up to early expectations of being a wonder drug, it is effective against a dozen or so conditions, including a type of leukemia, multiple sclerosis, hepatitis, and genital warts.

In another cytokine-based cancer treatment, certain T cells are removed from tumor samples, and incubated with interleukin-2, which the patient also receives intravenously. The removed T cells, activated by the cytokine, are injected into the patient. Interleukin-2 is also used to treat kidney cancer. In another approach, colony stimulating factors can boost the white blood cell supply in people whose immune systems are temporarily suppressed, such as those receiving drugs to treat cancer or AIDS.

Cancer treatment may soon consist of combinations of immune system cells and biochemicals, plus standard therapies. Immunotherapy can enable a patient to withstand higher doses of a conventional drug, or destroy cancer cells remaining after standard treatment.

The idea of using the immune system to treat cancer is not new. In 1893, a New York surgeon, William Coley, intentionally infected cancer patients with killed Streptococcus bacteria, after noticing that some patients with bacterial infections spontaneously recovered from the cancer. Sometimes Coley's toxins worked, although he did not understand precisely how. Today we know that an immune system biochemical called tumor necrosis factor is often responsible for the body's success in overcoming cancer. However, researchers do not yet understand all of this intriguing molecule's effects sufficiently to use it as an anticancer drug safely.

Copyright ©1998 The McGraw-Hill Companies. All rights reserved. Any use is subject to the Terms of Use and Privacy Policy.
McGraw-Hill Higher Education is one of the many fine businesses of The McGraw-Hill Companies.
For further information about this site contact mhhe_webmaster@mcgraw-hill.com.