Monoclonal Antibodies As Therapeutic Agents Essay

2024 words - 8 pages

Monoclonal Antibodies as Therapeutic AgentsWhat are antibodies?Antibodies are ideal for the use in drug therapies because they are very specific in the functions that they carry out in biological systems. They can be described as Y-shaped proteins that consist of four polypeptide chains. Residing in the arms of the Y are two identical light polypeptide chains and the stem of the Y consists of two heavy polypeptide chains. The light polypeptide chains that make up the arms are referred to as a Fab (Fragment for Antigen Binding) and function by recognising the antibody's target or antigen (antibody generating molecule). The stem of the Y is known as the Fc portion of the antibody. The stem's main role is to communicate with the human immune system so that it initiates a series of immunilogical responses. These initiated immunilogical responses include ADCC (Antibody Dependent Cellular Cytotoxicity) in which certain human immune system cells bind to the Fc via specific antibody binding receptors. These immune cells are then signalled to destroy the invading entity, a molecule or a whole cell, to which the antibody is bound. The complement system is another immune response that can be initiated, where a series of blood proteins bind to the Fc and subsequently elicit destruction of the invading target. An important factor in the efficacy of antibody therapeutics is that the Fc portion also provides for the long half-life of the antibody within the blood.The history of antibody research.In the late 1800's scientists discovered that blood serum which was taken from mice that were immunised (exposed to) with human proteins contained a mixture of mouse antibodies that could be used to combat certain diseases. This, however, was problematic in that there was no technology available at the time to produce sufficient quantities of the desired antibodies. In 1975, the Nobel Prize winning hybridoma technology was discovered by G. Kohler and C. Milstein. This then allowed scientists to produce large quantities of one particular antibody. A hybridoma is a cell line made by fusing and antibody producing B cell with a myeloma cell (a cancer cell capable of replicating nearly indefinitely in culture). Hybridomas, in addition to providing a stable cell line from which large quantities of antibody can be derived, also produce only a single type of antibody and are, therefore, referred to as monoclonal (mono-single, clone).The new hybridoma technology generated the possibility for scientists to use mouse monoclonal antibodies as human therapeutics. This, however, led to the discovery of another problem. When patients were injected with the new treatments, the human immune system, naturally, developed human antibodies directed toward the 'invading' mouse proteins. This human immune response is known as HAMA (Human Anti-Mouse Antibodies) and neutralises the mouse antibodies by the rapid clearance from the blood. Thus preventing the antibody from binding to its target...

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