An Investigation in Monoclonal Antibodies
One of the major medical concerns of the century has been finding a cure for cancer. Scientists have made progress in solving the cancer puzzle with the innovation of procedures such as chemotherapy and various scanning methods, but no one has yet found a definite solution. Possibly the newest discovery in the cancer field has been monoclonal antibodies (mAbs). Nicknamed “magic bullets,” mAbs have been proposed to be analogous to microscopic missiles that seek out concentrations of cancerous matter and attack. MAbs aren’t nearly this simple, but when working correctly they are very effective and are advantageous over normal antibodies or less specific polyclonals. These engineered antibodies have created a whole new area of research for scientists trying to find a cure for cancer, as well as for those who have found other applications for mAbs.
Structure and Function of Antibodies
Natural antibodies or immunoglobulins (Ig) are crucial protein molecules of the immune system that participate in fighting off invading microbes, viruses and toxins. Each antibody is made up of four chains that are linked by disulfide bonds. They are y-shaped peptide molecules with two split arms at one end of a molecule making up the FAb region, and one constant tail region, called the Fc region, making up the other end. The two arms provide the sites at which an antibody binds itself to an antigen or cancerous agent. Interactions with the cells of the immune system that engulf and eliminate invading microbes and viruses are done through the constant Fc region. Many antibodies coat an antigen at a given time, interacting through chemical signals and increasing the chances for an antigen’s destruction. Production of Monoclonal Antibodies
Georges J.F. Kohler and César Milstein won the Nobel Prize in 1984 for their experimental techniques that led to the innovation of monoclonal antibodies. The method proposed for creating mAbs has not changed significantly. However, newer technology is now available, allowing for better efficiency and accuracy during experimentation. Engineering of mAbs is started when an immunization of an antigen “X” (the desired target) is given to a mouse. This mouse soon gains immunity to the antigen in a similar manner to a human gaining immunity after receiving a vaccine. As a result, the mouse creates antibody secreting white blood cells called B-lymphocytes (myeloma cells) which are an integral part of the immune system. B-lymphocytes are formed by bone marrow stem cells and migrate into the circulation and lymphoid tissue. An antigen coming in contact with a B cell stimulates a chromosomal rearrangement in that B cell so that specific antibodies can be produced. After immunization, newly formed B-lymphocyte cells are removed from the spleen of the mouse, and they are promptly fused with antigen tumor cells from a tissue culture. This tumor-spleen cell combination is now called a hybridoma. Hybridoma technology is the basis for creating mAbs.
Large amounts of these hybridoma cells are taken through a screening process in which it is determined whether or not they produce antibodies for the correct antigen. The hybridomas that are determined to create the antibodies with a correct antigen binding structure are fished out a large stew of many others. Scientists now take the step of genetically manipulating hybridomas so that they are either fully humanized or so that are a hybrid containing partly human components and partly maurine or mouse components. However, it is still extremely difficult to remove all the maurine parts of the antibody without knowing the exact structure and properties of the target antigen. The next step in cultivating mAbs is the now humanized hybridomas and cloning them many times over. Cloned hybridomas are then isolated for their cultivation of mAbs....
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