Immune System Series

Frontiers in Immunology: Hybridoma Technology

Through a stratagem known as hybridoma technology, scientists are now able to obtain, in quantity, substances secreted by cells of the immune system-both antibodies and lymphokines. The ready supply of these materials has not only revolutionized immunology but has also created a resounding impact throughout medicine and industry.

A hybridoma is created by fusing two cells, a secreting cell from the immune system and a long-lived cancerous immune cell, within a single membrane. The resulting hybrid cell can be cloned, producing many identical offspring. Each of these daughter clones will secrete, over a long period of time, the immune cell product. A B-cell hybridoma secretes a single specific antibody.

Such monoclonal antibodies, as they are known, have opened remarkable new approaches to preventing, diagnosing, and treating disease. Monoclonal antibodies are used, for instance, to distinguish subsets of B cells and T cells. This knowledge is helpful not only for basic research but also for identifying different types of leukemias and lymphomas and allowing physicians to tailor treatment accordingly. Quantitating the number of B cells and helper T cells is all-important in immune disorders such as AIDS. Monoclonal antibodies are being used to track cancer antigens and, alone or linked to anticancer agents, to attack cancer metastases. The monoclonal antibody known as OKT3 is saving organ transplants threatened with rejection, and preventing bone marrow transplants from setting off graft-versus-host disease.

monoclonal antibody

Monoclonal antibodies are essential to the manufacture of genetically engineered proteins (Genetic Engineering); they single out the desired protein product so it can be separated from the jumble of molecules surrounding it. monoclonal antibodies are also the key to developing new types of vaccines (Vaccines Through Biotechnology).

With growing experience, scientists have devised several sophisticated variants on the monoclonal antibody. For instance, they have created some monoclonal antibodies of human rather than mouse origin; human monoclonal antibodies can be used for therapy without risking an immune reaction to mouse proteins. They have also succeeded in "humanizing" mouse antibodies by splicing the mouse genes for the highly specific antigen-recognizing portion of the antibody into the human genes that encode the rest of the antibody molecule.

Other monoclonal antibodies have been designed to behave like enzymes; these so-called catalytic antibodies or abzymes speed up, or catalyze, selected chemical reactions by binding to a chemical reactant and holding it in a highly unstable "transition state." By, in fact, cutting the proteins to which they bind, such antibodies may be useful for such things as dissolving blood clots or destroying tumor cells. Yet other researchers, by fusing two hybridoma cells that produce two different antibodies, have created hybrid hybridomas that secrete artificial antibodies made up of two nonidentical halves. While one arm of the bispecific antibody binds to one antigen, the second arm binds to another. One may bind to a marker molecule, for instance, and the second to a target cell, creating an entirely new way to stain cells. Or, one arm of a chimeric antibody may bind to a killer cell while the other locks to a tumor cell, creating a lethal bridge between the two.