Advantages and issues of monoclonal antibodies for therapeutic purposes (Part 3- mAbs)
Welcome to the 3rd part of the 19-part series on monoclonal antibodies (mAbs). You can read the first and second parts to understand what are monoclonal antibodies and how they are produced.
Advantages over conventional drugs
As already discussed, monoclonal antibodies are identical antibodies that recognize a single specific epitope on an antigen. This property of monoclonal antibodies can make them useful for therapeutic purposes and more effective than conventional drugs.
The conventional drugs not only attack the foreign pathogen or diseased cells, but they also attack the body’s cells that cause serious side effects. On the other hand, therapeutic monoclonal antibodies target only the foreign antigen or the specific protein markers on the target cells. For instance, in the case of cancer treatment, monoclonal antibodies are developed to bind to the proteins present specifically on the tumor cells. After binding, the antibodies tag the target cancerous cells for destruction by the immune system.
This property of monoclonal antibodies makes them very suitable for therapeutic use in many diseases such as cancer, genetic disorders, HIV, autoimmune diseases, etc. Furthermore, since the therapeutic monoclonal antibodies bind only to the intended target cells, therefore there are very few unexpected side effects while using them.
Issues of mouse monoclonal antibodies
One major issue in generating antibodies for therapeutic purposes is that most monoclonal antibodies are produced in mice through the Hybridoma Technology developed by Kohler and Milstein in 1975.
There are many clinical applications in which the mouse monoclonal antibodies are useful like in diagnostic and research purposes. However, when mouse monoclonal antibodies are introduced into the patients, the isotypic determinants of mouse antibodies are recognized as foreign by the patients’ bodies.
As a result, the patients generate an antibody response or anti-antibodies against the isotypic determinants on the foreign mouse antibody. Thus, clearing the mouse monoclonal antibodies from the bloodstream. In addition to this, circulating complexes of mouse and human antibodies can also cause allergic reactions. In some cases, these complexes can accumulate in organs such as the kidneys and cause severe and even life-threatening reactions.
To minimize the complications resulting from using mouse monoclonal antibodies in humans, scientists are undertaking a significant effort to engineer monoclonal antibodies with recombinant DNA technology.
Antibody engineering
With the knowledge of antibody structure and antibody regulation, three types of therapeutic antibodies have been engineered. These are:
· chimeric monoclonal antibodies (discussed in Part 4),
· humanized monoclonal antibodies (discussed in Part 5)
· and fully human monoclonal antibodies (discussed in Part 6).
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