Explain how Monoclonal Antibodies can be produced and how they can be used to target specific cells and chemicals.

Rohit Gumber

Animals have the ability to recognise foreign and harmful molecules entering their bodies. Efforts are made to isolate and expel such foreign molecules. The immune system is the major defence mechanism against substances that have gained entry. A substance capable of initiating an adaptive immune response is called an "antigen". The body's reaction to the recognition of this antigen is to manufacture a protein called an antibody. An antibody, recognising an antigen, links to it by a series of chemical bonds. These bonds are individually very weak (non-covalent) but their number overcomes this weakness. The locking of an antibody and its antigen is a bit like the linking of enzymes and substrate. The combination of the two molecules sets in motion a series of events within the body, which results in the elimination of the antigen from the body.

For certain laboratory research it is useful to have a pure preparation of antibodies with single specificity. These types of antibody are called ‘monoclonal antibodies’. Monoclonal antibodies do not differ structurally from other natural antibodies. The property that makes monoclonal antibodies unique is that all the molecules in any single preparation are identical. Their reaction with any antigen is also exactly the same each time. It is this constancy in preparation and in their effect that makes them so useful. Immunologically complex structures such as cell surfaces may be dissected at a molecular level and studied, piece by piece. The knowledge gained has a tremendous impact on our understanding of many diseases and the way in which they are treated

In order to obtain an unlimited supply of a defined antibody to an antigen in the laboratory, all that is required is the isolation and immortalisation of the relevant B-lymphocytes from an animal. The clone could be isolated and grown under laboratory conditions by cell culture. In this way, the cloned B-lymphocytes would continue to produce the antibody, which could be collected from the culture. However, most attempts to grow clones of B-lymphocytes in the laboratory have failed. What is required therefore is to develop some method by which antibody producing B-lymphocytes can grow freely and well in laboratory ...

This is a preview of the whole essay

In 1975, Köhler and Milstein demonstrated that mouse tumour cells could be fused with B-lymphocytes and the resultant hybrids produced antibodies. When the fusion process is complete, the daughter cells are known as "hybridomas”. The characteristics required are immortality from the tumour cell and antibody production from the B-lymphocyte. Thus, hybridisation techniques allow immunoglobulin-producing cells to be immortalised. However, they do not determine which lymphocyte is being immortalised. To achieve this Köhler and Milstein developed the technique of immunising their experimental animal with the relevant antigen by injection. After several weeks, the mouse's immune system would be producing its own clones of B-lymphocytes that were capable of producing antibodies that recognised the test antigen. The mouse lymphocytes were collected from its spleen and were used in the fusion process with the tumour cells. In this way, it was likely that many of the lymphocytes fused would be secreting the antibody against the antigen of interest. However, using techniques such as this, in which the animal is injected to produce specific antibodies, many lymphocytes will be fused which are producing irrelevant antibodies. When the successful hybridisation of tumour cells and B-lymphocyte takes place, the different cells can be cultured separately and clones of hybridoma cells, all producing one specific antibody are made, these antibodies are called monoclonal.

The use of monoclonal antibodies has become a valuable tool in biology and medicine because pure lines of antibody can combine with and therefore mark, or identify, the component substances of cells and tissues. Monoclonal antibodies can play a role in identifying antigens present in minute quantities, such as those that may be present on cancer cells. They target and bind to antigens in the body which may trigger a patient’s natural defences, which then attack and destroy the foreign material. In addition, monoclonal antibodies can be therapeutically active on their own, or can be attached to chemotherapeutic agents, toxins, or radioisotopes that may enhance destruction of the target cell. Under investigation is the use of monoclonal antibodies for immunisation, for typing tissue used in transplants and for targeting drugs to specific sites in the body.

Monoclonal antibodies are immunoglobulins that are of immense value and interest because the method of their production allows the manufacture of endless quantities of a single antibody against an antigen which may be specially selected. This not only allows us to make advances in our understanding of the basic principles of the working of the immune system, but also offers the possibility that such knowledge will enable new methods of diagnosis and therapy to be created.

Bibliography