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Feb 1, 2011 (Vol. 31, No. 3)

GEN's 30th Anniversary: mAb Therapeutics

  • Panel of Specificities

    The monoclonal antibodies for which Ortho received the patents were developed by Dr. Gideon Goldstein. An M.D. and Ph.D.,. Goldstein is well known for the isolation of thymopoietin, a thymic hormone which restores balance to the immune system. He joined Ortho Pharmaceutical Corp. in 1977 and is now vice president of the Immunobiology Division.

    The nine monoclonals work as a panel; each identifies a specific type of lymphocyte. One labeled OKT3, for example, reacts with all mature lymphocytes, while OKT4 is targeted to the suppressors. Thus monoclonal antibodies, themselves a product of the immune system, are being used to locate and study the component cells of the immune system itself.

    Sequential testing with the panel of monoclonal antibodies can reveal patterns of preservation and change in the state of the immune system. The helpers and suppressors they identify interact as partners to keep the immune system in balance, or homeostasis. Normally there are about twice as many helpers as suppressors. In disease states, however, this 2:1 ratio may change dramatically. Monoclonal antibodies which seek out the different types of T cells enable researchers to count the number of T cells of a certain class, like helpers or suppressors, in the body. Changes in the relative size of these cell populations may indicate a certain disease state, much as a fingerprint helps identify a person.

    In rheumatoid arthritis, for example, the ratio of helper to suppressor cells may increase to as much as 5:1. So many helper T cells are stimulating antibody production by B cells that antibodies begin to attack the body’s own tissues.

    In the case of AIDS, however, the ratio is reversed. The number of suppressors increases, inhibiting the body’s resistance to infection.

    Another diagnostic application for which various monoclonal antibodies are being clinically tested is in immunodeficiency disease states such as leukemia and lymphoma. By enabling physicians to monitor changes in the body’s immune system more precisely, monoclonals may help minimize the use of conventional chemotherapy and radiation treatments, which kill some healthy tissues and can have undesirable side effects, such as loss of hair or nausea.

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