Monoclonal Antibodies

A tumor of plasma cells (myeloma or plasmacytoma) is monoclonal and therefore produces antibodies of a single specificity. In most cases, the specificity of the tumor-derived antibody is not known, so the antibody cannot be used to specifically detect or bind to molecules of interest. However, the discovery of monoclonal antibodies produced by these tumors led to the idea that it may be possible to produce similar monoclonal antibodies of any desired specificity by immortalizing individual antibody-secreting cells from an animal immunized with a known antigen. A technique to accomplish this was described by Georges Kohler and Cesar Milstein in 1975 and has proved to be one of the most valuable advances in all of scientific research and clinical medicine. The method relies on fusing B cells from an immunized animal (typically a mouse) with a myeloma cell line and growing the cells under conditions in which the unfused normal and tumor cells cannot survive (Fig. 5-9). The resultant fused cells that grow out are called hybridomas; each hybridoma makes only one Ig. The antibodies secreted by many hybridoma clones are screened for binding to the antigen of interest, and this single clone with the desired specificity is selected and expanded. The products of these individual clones are monoclonal antibodies that are each specific for a single epitope on the antigen or antigen mixture used to identify antibody-secreting clones.

Monoclonal antibodies have many practical applications in research and in medical diagnosis and therapy. Some of their common applications include the following:

• Identification of phenotypic markers unique to particular cell types. The basis for the modern classification of lymphocytes and other leukocytes is the recognition of individual cell populations by specific monoclonal antibodies. These antibodies have been used to define clusters of differentiation (CD) markers for various cell types (see Chapter 2).

• Immunodiagnosis. The diagnosis of many infectious and systemic diseases relies on the detection of particular antigens or antibodies in the circulation or in tissues by use of monoclonal antibodies in immunoassays (see Appendix IV).

• Tumor detection. Tumor-specific monoclonal antibodies are used for detection of tumors by imaging techniques and by staining tissues with labeled antibodies.

• Therapy. Advances in medical research have led to the identification of cells and molecules that are involved in the pathogenesis of many diseases. Monoclonal antibodies, because of their exquisite specificity, provide a means of targeting these cells and molecules. A number of monoclonal antibodies are used thera-peutically today (Table 5-3). Some examples include

Isolate spleen cells from mouse immunized with antigen X

Antigen X

Mixture of spleen cells including some producing anti-X antibody

Mixture of fused and unfused cells

Mutant myeloma line; unable to grow in HAT selection medium; does not produce antibody

In vitro selection in HAT medium

Only fused cells (hybridomas) grow

✓ I

1 v

_ Isolate clones derived from single cells_

y j

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