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Immunotherapy

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 foreign tissue, would be ideal magic bullets. Immunotherapy uses immune system components to fight disease — both the humoral immune response (antibodies) and the cellular immune response (cytokines).

Monoclonal

Antibodies-

Targeting 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 antigen-laden 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 (fig. 16A).

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 go-nadotropin (see chapter 22, p. 916), 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.

MAbs can ferry conventional cancer treatments to where they are needed and limit their toxicity by sparing healthy tissue. Drugs or radioactive chemicals are attached to MAbs that deliver them to antigens on cancer cells. When injected into a patient, the MAb and its cargo are engulfed by the cancer cells, which are destroyed. Although MAbs were originally derived from mice, human versions that prevent allergic reactions are now available.

Cytokines

Immunotherapy experiments were difficult to do in the late 1960s because cytokines and antibodies could be obtained only in small amounts from cadavers. In the 1970s, recombinant DNA and monoclonal antibody technologies made it

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