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How Monoclonal Antibodies Work

Today scientists use MAbs to identify and measure minute quantities of hormones, infectious substances, toxins, and other molecules in tissues and fluids. MAbs can also be used to identify malignant cells (cells with abnormal growth) in tissues. For example, to help diagnose cancers hidden in the body, radioactive substances are attached to MAbs that recognize and target cancer cells. These MAbs are then injected into a patient’s body. The MAbs find cancer cells for which they are targeted and bind to them. A special machine that uses film sensitive to radioactivity is used to take an internal picture of the patient’s body. This image reveals any cells to which the MAbs attached, indicating the presence of cancer. In November 1997, the Food and Drug Administration approved the first MAb to be used for treating cancer in the United States. This antibody, in the form of a drug called rituximab and marketed under the brand name Rituxan, will be used to treat non-Hodgkins lymphoma, a cancer of B cells.

Researchers use MAbs created to target a muscle protein called myosin to assess the extent of damage to the heart muscle after a heart attack. Myosin exists in large quantities in healthy muscle tissue. When MAbs for myosin are injected into the heart muscle of a heart-attack patient, the MAbs bind to any remaining myosin, enabling researchers to determine how much of this protein was lost during the heart attack, an indication of the extent of heart damage. MAbs targeted for a blood protein called fibrin, which is produced when blood coagulates, can locate the site of blood clots in a patient. MAbs can also be used to determine whether the tissue of a potential organ donor is compatible with the tissue of a recipient. After a patient receives an organ transplant, different MAbs can then be used to help prevent the patient’s immune system from rejecting the new organ. For example, a MAb known as OKT3 recognizes and blocks a substance on T lymphocytes, the cells that regulate rejection of foreign tissue. When OKT3 is given to the recipient of a transplant, the patient’s immune response against the foreign tissue is suppressed, increasing the chances that the transplant will be successful.

One well-known example of a MAb-based technology is the home pregnancy kit. In one version of this test, a MAb specific for human chorionic gonadotropin (HCG), a hormone elevated in urine only during pregnancy, is purified and bound to a plastic test tube. A urine sample is collected and added to the tube, and if HCG is present, the MAb attaches to it. A second MAb, also specific for HCG, is then added. This second MAb has an additional molecule linked to it, such as an enzyme that changes the color of the urine in the final step of the test. In the absence of HCG in the urine, the second purified antibody will not be bound and no change in urine color will occur.

MAbs can also be used to diagnose the human immunodeficiency virus (HIV) that causes AIDS. A laboratory test determines whether an individual is producing antibodies against HIV. In this test, a MAb is used to test the blood of a patient for the presence of another type of antibody that binds to the virus. Only patients who have been exposed to HIV will have the second type of antibody in their blood.

MAbs are currently studied for their ability to carry drugs and other substances to specific sites in the body. For example, MAbs that attach to tumor cells can also carry radioactive substances, drugs, or toxins. When injected in patients, these armed antibodies, or immunoconjugates, selectively seek out and destroy the disease-causing cells while sparing normal tissue. The MAb in the immunoconjugate locates and attaches to the tumor cell, while the toxic substance, known as the payload, destroys the cell. An immunotoxin is an immunoconjugate that links a MAb with a specific, toxic protein molecule derived from a plant such as ricin (from the seeds of castor beans) or from bacteria such as diphtheria. Researchers believe that immunotoxins will one day be used routinely to fight cancer, parasitic infections, allergies, and other diseases of the immune system.