Monoclonal Antibodies- Types, Uses and Limitations

Monoclonal antibodies

They are antibodies that are made by identical immune cells that are all clones of a unique parent cell. Monoclonal antibodies can have monovalent affinity, in that they bind to the same epitope.

A technique to produce monoclonal antibodies was devised by Georges Kohler and Cesar Milstein in 1975. The method relies on fusing B cells from an immunized animal (typically a mouse) with an immortal myeloma cell line and growing the cells under conditions in which the unfused normal and tumor cells cannot survive. The resultant fused cells that grow out are called hybridomas; each hybridoma makes only one Immunoglobulin, derived from one B cell from the immunized animal. 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, each specific for a single epitope on the antigen used to immunize the animal and to identify the immortalized antibody-secreting clones.

Monoclonal Antibodies- Types, Uses and Limitations

Types of monoclonal antibodies

  1. Naked Monoclonal Antibodies: There is no drug or radioactive material attached to them. 
  2. Conjugated Monoclonal Antibodies: Monoclonal antibodies joined to a chemotherapy drug or to a radioactive particle are called conjugated monoclonal antibodies.
  3. Bispecific Monoclonal Antibodies: These drugs are made up of parts of 2 different monoclonal antibodies, and they can attach to 2 different proteins at the same time. 

Uses of monoclonal antibodies

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

  1. 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 These antibodies have been used to define clusters of differentiation (CD) markers for various cell types.
  2. The diagnosis of many infectious and systemic diseases relies on the detection of particular antigens or antibodies in the blood, urine, or tissues by use of monoclonal antibodies in immunoassays.
  3. Tumor identification. Labeled monoclonal antibodies specific for various cell proteins are used to determine the tissue source of tumors by staining histological tumor sections.
  4. 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 therapeutically. Some examples include antibodies against the cytokine tumor necrosis factor (TNF) used to treat rheumatoid arthritis and other inflammatory diseases, antibodies against CD20 for the treatment of B cell leukemia and for depleting B cells in certain autoimmune disorders, antibodies against epidermal growth factor receptors to target cancer cells, antibodies against vascular endothelial growth factor (a cytokine that promotes angiogenesis) in patients with colon cancer etc.
  5. Functional analysis of cell surface and secreted molecules. In biologic research, monoclonal antibodies that bind to cell surface molecules and either stimulate or inhibit particular cellular functions are invaluable tools for defining the functions of surface molecules, including receptors for antigens. Monoclonal antibodies are also widely used to purify selected cell populations from complex mixtures to facilitate the study of the properties and functions of these cells.

Limitations of monoclonal antibodies

Monoclonal antibodies are most easily produced by immunizing mice, but patients treated with mouse antibodies may make antibodies against the mouse Ig, called human anti-mouse antibody (HAMA). These anti- Ig antibodies block the function or enhance clearance of the injected monoclonal antibody and can also cause a disorder called serum sickness.

Genetic engineering techniques have been used to expand the usefulness of monoclonal antibodies. The complementary DNAs (cDNAs) that encode the polypeptide chains of a monoclonal antibody can be isolated from a hybridoma, and these genes can be manipulated in vitro.

Fully human monoclonal antibodies are also in clinical use. These are derived using phage display methods or in mice with B cells expressing human Ig transgenes. Humanized antibodies are far less likely than mouse monoclonal to appear foreign in humans and to induce anti-antibody responses.

Monoclonal Antibodies- Types, Uses and Limitations

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