2.6.5 Monoclonal Antibodies

Diagnostic uses of monoclonal antibodies

• Monoclonal antibodies can be used diagnostically for:
  • Pregnancy tests
  • Diagnosing HIV
  • Detecting the presence of pathogens such as Streptococcus bacteria
  • Distinguishing between Herpes I and Herpes II
  • Blood typing before transfusions and tissue typing before transplants
  • Detecting the presence of antibiotics in milk
  • Detecting cancer cells

• Monoclonal antibodies can also be used to locate the position of blood clots for patients thought to have deep vein thrombosis. This occurs by:
  • Injecting a mouse with human fibrin (the main protein found in blood clots)
  • This activates the plasma cells to produce antibodies against fibrin
  • These cells are collected from the mouse spleen
  • The plasma cells are then fused with tumour cells forming hybridomas that produce antifibrin antibodies
  • To detect where the antibodies are binding to fibrin molecules, a radioactive chemical (producing gamma radiation) is attached to the antibodies making them radioactively labelled
  • A gamma-ray camera is used to detect where these radioactively labelled antibodies have attached to a fibrin molecule, hence indicating where blood clots can be found

• Generally monoclonal antibodies are used only once

Another example of the diagnostic use of monoclonal antibodies - test for HIV

Therapeutic uses of monoclonal antibodies

• Therapeutically monoclonal antibodies have multiple applications to include:
  • Treatment for the rabies virus, (which can be potentially fatal), by injecting purified antibodies
  • The prevention of transplanted organ rejection, achieved by intervening with the T cells involved in the rejection process
  • Autoimmune therapies for allergic asthma and rheumatoid arthritis; here monoclonal antibodies are able to bind and deactivate factors involved in the inflammatory response
  • Treatment for diseases caused by the overproduction or inappropriate production of B-cells (eg. leukaemia, multiple sclerosis and myasthenia gravis); the antibody (rituximab) binds to cell surface receptor proteins on B-cells (not plasma cells) and causes the death of the cells
  • Prevention of blood clotting following angioplasty procedures; here monoclonal antibodies bind to receptors on the platelet surface thereby inhibiting fibrinogen from binding and subsequent clotting from ensuing
  • Targeted treatment of breast cancer; Herceptin (trastuzumab) is a monoclonal antibody used to treat breast cancer, it recognises receptor proteins on the surface of cancer cells and binds to them allowing the immune system to identify and destroy them
  • Treatment of melanoma (a type of skin cancer); the antibody (ipilimumab) binds to a protein produced by T-cells (whose role is to reduce the immune response) which results in the immune system remain active against the cancer cells

• Using monoclonal antibodies as a treatment requires multiple administrations and this can cause problems
• Initially the monoclonal antibodies were produced by mice, rabbits or other laboratory animals (as these were easier to produce), however this triggered an immune response when they were introduced to humans
• Scientists have largely overcome this by:
  • Genetically modifying the antibody polypeptide chains so that the amino acid sequences are now human not mouse or rabbit sequences
  • Altering the type and position of the sugar groups (antibodies are glycoproteins) attached to the heavy polypeptide chains to reflect those found on human antibodies