When monoclonal antibodies are mentioned, they refer to proteins produced by a very specific cell line or clone. Their specific properties include having only a single antigenic determinant. The production of the material used for immunization originates from a single B lymphocyte.
What is a monoclonal antibody?
Once an antigen is captured by an antibody directed to it and forms a bond with it, it is referred to as an epitope. Normally, multiple structures on a viral, bacterial, or other pathogen surface are present on an epitope, so that they each react with very specific antibodies and cause a defense system in the organism. This results in a whole mixture of antibodies, including various B lymphocytes for the formation of cones, which are then activated and multiplied. B lymphocytes are part of the white blood cells and are alone capable of binding antibodies in the organism. Therefore, they constitute an essential part of the immune system. In this process, they are carriers of information for the formation of a counter-reaction and, when activated by antigens foreign to the body, they can transform into plasma cells, which then produce sufficient antibodies. Monoclonal antibodies, on the other hand, are highly specific against only one determinant of the pathogen and are therefore generated from a B lymphocyte by hybridoma technology. Here, monoclonal antibodies are formed by cell fusion between lymphocytes and tumor cells, and the latter can divide indefinitely. This, in turn, makes cultivation and ultimately efficacy in drugs and antibiotics possible once human monoclonal antibodies are used, for example, against infectious diseases. Such antibodies would also be useful in the diagnosis of tumors, whereby degenerate cells can be detected via an altered surface.
Pharmacological action
To diagnose pathogens, it is necessary to define certain features of the immune defense. These can be detected on the surface. Once an organism uses its immune system to initiate defense reactions, B lymphocytes are animated to produce antibodies. From this, a collection of antibodies with different properties is formed, while the respective division in turn forms a B-cell clone, whose antibodies react to a possible antigen. In order to be able to produce monoclonal antibodies, a method developed by the Nobel Prize winners Cesar Milstein and Georges Köhler and published together with Niels Jerne in 1975 is used. Using the method they developed, it was possible to produce a specific type of antibody, which in turn made cultivation in the test tube feasible, not only in any quantity, but also with very specific characteristics of the antibodies, which are then suitable for use in drugs. As a result of the process, the immune cells are more robust and can also survive as an attached culture. Because the fusion of tumor and immune cells results in a remarkably unlimited growth rate, this cell is called a hybridoma cell.
Medical application and use
Once degenerate B cells with a permanent ability to divide fuse with B cells that produce antibodies, monoclonal antibodies that are genetically identical are produced. Such hybridomas are structurally identical and are designed to recognize only a very specific feature, hence the term “monoclonal.” Production in the pharmaceutical field is very difficult and is mainly tested on mice in research. In this process, antigens are injected into the animal to trigger immunization. Of particular interest are the B lymphocytes in the spleen, which are cultured as cells and fused with myeloma cells. The latter are those degenerate lymphocytes that form tumors. An enzyme that hybridizes nucleic acid then ensures that hybrid cells are formed. The fusion of the immortal tumor cells and B cells in their antibody production produces the enormous quantity, which are then grown as cell colonies by selection of different cell clones and form one and the same antibody over and over again. These can be used for medical therapy in a targeted manner, for example to diagnose carcinogens and tumors. Monoclonal antibodies are now also used to treat transplant rejection.
Risks and side effects
For several years now, the use of monoclonal antibodies has been clinically proven and represents a new and growing area in pharmaceutical development. Among these, passive vaccines have proven successful, such as snake venom immune sera, tetanus immune globulin, or digitalis antioxin. The complex mixture and extraction of such antibodies is not carried out from the blood itself, but as a molecular biological synthesis of proteins. Only immunoglobulin G is suitable for drugs, as it is ypsilon-shaped and thus facilitates the development of antibodies. In cancer therapy, monoclonal antibodies in use aim to cause dissolution of the degenerate cells, blocking growth factor signaling pathways, including in the formation of new blood vessels. If therapy is unresponsive, the B cells can then be removed from the patient’s blood again by a rituximab infusion. In joint diseases, such as rheumatoid arthritis, the inflammatory processes are also triggered and intensified by antigens, which eventually leads to the dissolution of bone and joint tissue. A new balance is created by antibodies, which specifically intervene in the inflammatory process. Finally, the use of monoclonal antibodies is also applied in microbiological diagnostics. Parasitic, bacterial or viral infections can thus be better detected and identified because the pathogens can label them. Recombinant agents are only approved for treatment when therapy has previously been unsuccessful and disease-modifying agents have become necessary. There is a risk that treatment may lead to increased incidences of new infections. This is because, although monoclonal antibodies recognize specific protein structures by mimicking them, they remain proteins themselves, administered only by infusion or injection by the physician. Reactions that occur are side effects at the injection site, including, for example, skin reactions or allergies.
