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.