The Industrial Production of Monoclonal Antibodies in Cell Culture
The development of the hybridoma technique by Kohler and Milstein in 1975 made it possible to produce for the first time monoclonal antibodies of constant and defined specificity in potentially unlimited quantities. Monoclonal antibodies have become important tools in the research laboratory and have attracted widespread commercial interest. In the field of diagnostics there has been a rapid development of assay systems based on monoclonal antibodies for the detection and measurement of, for instance, drugs, hormones, infectious diseases and blood group antigens (Nowinski et al., 1984; Voak and Lennox, 1983). The feasibility of using suitably labelled antibodies to diagnostically “image” tumor tissues in vivo is being actively investigated by a number of groups (see for example Mach et al., 1981). It is recognised that if monoclonal antibodies can be used to detect tumor tissue in this way then they may also be useful in therapy, for instance, as a means of delivering cytotoxic agents specifically to cancer cells (Marx, 1982- Vitella, 1982; Miller, 1982). Another exciting application which exploits the extreme specificity of the antibody-antigen interaction is immunopurification. This method is particularly useful for the purification of high value products such as interferon (Secher and Burke, 1980) which may be present in dilute solution in crude mixtures. We anticipate this technique becoming more widely applied as antibodies become more readily available and less expensive (Hill et al., 1985). The increased application of monoclonal antibodies has resulted in a need to produce large quantities (grams to kilograms per year) at appropriate cost. This has led our group and others to develop new production methods. Our own developments in fact arose from the need to produce monoclonal ABO blood typing reagents (Voak and Lennox, 1983) and these were the first bulk monoclonal products to reach the market.
KeywordsDilution Rate Draught Tube Maximum Specific Growth Rate Oxygen Transfer Rate Chemostat Culture
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