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Monoclonal Antibiotics


How Were Monoclonal Antibodies Discovered?

Monoclonal Antibodies originated in 1975, when British scientists Dr. César Milstein and Dr. Georges Köhler developed a process for generating unlimited quantities of pure, uniform mouse antibodies designed to target specific proteins. This process that they came up with was called somatic cell hybridization. The process involved fusing myeloma cells with antibody-secreting B cells from an immunized mouse, which resulted with a hybridoma cell. What these scientists were able to do was create a cell that had the unlimited growth potential of a myeloma cell as well as the predetermined antibody specificity of a normal immune spleen cell. When a hybridoma produced the desired antibody, it would be subject to grow in a cell-culture where it would divide into monoclonal antibodies. Milstein and Köhler were awarded the 1984 Nobel Prize for Physiology and Medicine, for their pioneering work of monoclonal antibodies.


The technique that Milstein and Köhler used was called somatic cell hybridization. They did their experiment by using mice. First the spleen cells of the mouse that had been immunized with the desired antigen were fused with myeloma cells. The cell fusion mixture, or the hybridomas, is then transferred to a culture medium, which is also known as the HAT medium because it contains hypoxanthine, aminopterin, and the pyrimidine thymidine. At this stage the supernatants from the culture are tested for the desired antibody. Since the original culture may have started with more than one hybridoma cell, it is vital to isolate single cells and then allowing them to subculture. After the new cultures have grown, the supernatants from the new culture are tested to determine the hybridomas with the desired antibody. Each subculture now has monoclonal antibodies for the desired antibody because they are derived form a single cell. Hybridoma cultures can be maintained either in vitro, in culture vessels, or either in vivo, where they actually grow inside the mouse.