Immunology

Monoclonal antibodies (Uses )

Applications of monoclonal antibodies

Monoclonal antibodies are immunoglobulins that are made by identical immune cells that are all clones of a unique parent cell. They have many practical applications in research, medical diagnosis and therapy. Some of their common applications include the following:

 

Tumor identification: Labeled monoclonal antibodies specific for various cell proteins are used to determine the tissue source of tumors by staining histological tumor sections. On injecting into a person’s body, they will bind with cancer cells and clump them together. This makes it easier to identify a cancerous tumor, which can be then treated or removed.

Tumor detection

 

Treatment of Cancer:  Besides diagnosis of cancer and identification of tumor cells, these immunoglobulins have also been used in treatment of cancer.

Monoclonal antibodies have also been designed to treat cancer by:

  • Carrying drugs that have been attached to them, to the tumor so that the drugs specifically target cancer cells and can allow smaller doses of chemotherapy drugs to be used thus  reducing the side effects and risk to healthy cells.
  • Encourage immune system to attack the cancer cells directly.

 

Therapy: Identification of cells and molecules that are involved in the pathogenesis of many diseases have been made easier by advances in medical research. Monoclonal antibodies, because of their exquisite specificity, provide a means of targeting these cells and molecules. A number of them are used therapeutically.

E.g. Basiliximab is used in transplant rejection, Belimumab is used on treatment of systemic lupus erythematous.

Some other examples include

  • Antibodies against CD20 for treatment of B cell leukemia and depleting B cells in certain autoimmune disorders.
  • Antibodies against epidermal growth factor receptors to target cancer cells.
  • Antibodies against cytokine tumor necrosis factor (TNF) to treat rheumatoid arthritis and other inflammatory diseases.
  • Antibodies against vascular endothelial growth factor (a cytokine that promotes angiogenesis) in patients with colon cancer etc.

 

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. They   have been used to define clusters of differentiation (CD) markers for various cell types.

 

Immunodiagnosis: 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. E.g. Diagnosis of Cancer, Hormonal disorders such as thyroid disorders, Deep vein thrombosis (Blood clot in Vein), Atherosclerosis (Thickening and loss of elasticity of arterial walls).

 

Protein Purification: Monoclonal antibodies can be produced for any protein and can be conveniently used for the purification of the protein against which it was produced.

 Advantages

  • Specificity to bind to the desired protein.
  • Efficient elution from the chromatographic column.
  • High degree of purification e.g. About 5,000 fold purification of interferon-α2 is achieved than other techniques.

The disadvantage being 100 % purity cannot be achieved as these antibodies leaks into elution. They cannot even distinguish between intact target protein and fragment of it.

 

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.

 

Pregnancy Test: In pregnancy test kit, monoclonal antibodies have been designed to bind with a hormone called HCG which is found only in the urine of pregnant women. Antibodies attached to the end of a pregnancy test stick will cause a change in color or pattern which will indicate pregnancy if HCG is present in her urine.

 

Limitations

There are certain limitations of using monoclonal antibodies which are:

  • These 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. They can also lead to hypersensitivity reactions.

 

  • All the cancer cells may not carry the same antigen for which antibodyhas been produced. Thus, some cancerous cells may not be detected.

 

  • The free antigens (of target cells) present in the circulation may bind prevent them from their action on the target cells.

 

  • These antibodies can have some side effects such as allergic reactions, chills, weakness, rash, vomiting, diarrhoea, shortness of breath, headache etc.

 

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.