For mAb therapeutics, IgG is presently the only class of antibodies utilized. The most abundant IgG is then further divided into four subclasses based on their properties (namely, the location and quantity of disulfide bonds). Each antibody class performs a unique function in human biology. The five antibody classes (as classified by heavy chain sequence) are IgM, IgD, IgG, IgE, and IgA. Common suffixes include -omab, -ximab, -zumab, and -umab, representing murine, chimeric, humanized, and human agents, respectively. The nomenclature of mAbs depends on the origin of each respective mAb. An example of mAbs generated by recombinant DNA methodologies includes adalimumab. The culmination of all methodologies has led to present-day mAbs production capable of producing fully human mAbs and minimizing the risks originally associated with their predecessors. Examples of humanized mAbs include Daclizumab and trastuzumab. Chimeric clones were followed by developing "humanization," a process where murine protein loops (which served as ligand binding sites) were implanted within human immunoglobulins. Examples of chimeric mAbs include infliximab and rituximab. Chimeric clones were the next developments, whereby human crystallizable fragment (Fc) regions were attached in place of murine ones. ĭespite the initial challenges associated with murine methodologies of mAb development, research continued, and the development of alternative methods overcame these limitations. The increased clearance due to HAMA generation was also accompanied by eventual Immunoglobulin E (IgE) development and anaphylactic reactions on subsequent administrations. These hybrid cells allowed Kohler and Milstein to reliably produce a single antibody clone in large volumes and with a pre-selected specificity, which became known as mAbs. The initial biotechnology of primitive mAbs became quickly problematic when the murine origin of such proteins caused them to become immunogenic and non-sustainable for long-term therapy due to the development of human anti-murine antibodies (HAMA). Kohler and Milstein utilized these principles to conceive what came to be called a "hybridoma" (a fusion cell composed of myeloma cells and splenic B lymphocytes, both murine in origin). The antibodies generated by this immune response are proteins that have high specificity and affinity for the antigen/ molecule they were generated against. The concept of mAbs as therapeutic options is modeled after the immune system, particularly the humoral immunity (i.e., antibodies) generated by the immune system in response to foreign antigen exposure. It was not until 1975 when the generation of mAbs for use in humans was established by Drs Kohler and Milstein. Edward Jenner in 1796, when he inoculated pustular fluid from smallpox lesions to elicit immunity in the recipient. The earliest documented use of (indirect) antibody therapy was by Dr. As an example, a disease such as cancer can be evaluated for the presence of certain properties (i.e., hormone receptors in breast cancers), which can, in turn, be targeted by mAbs to provide a "tailored" therapy. Monoclonal antibodies (mAbs) are a prime example of personalized therapeutics enabled by advances in our knowledge of immunology, molecular biology, and biochemistry. Modern-day medicine has been revolutionized to be personalized and specific based on individualized specific disease characteristics.
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