Hybridoma and Myeloma Cell Lines

Since Kohler and Milstein (30) discovered the technique to produce immortalized, antibody-secreting cells—hybrid-omas—the development in this area has had a major impact on the production and application of the secreted proteins (mAb). Therefore, it is not surprising that this tool occupies an important and still growing place in industrial biotechnology because the range of applications is constantly expanding. The advantages of hybridomas and myelomas (i.e., their natural secretory ability and, as lymphocytes, growth in suspension) renders these cell lines ideal for exploitation in biotechnical processes.

To optimize the production of mAb, efforts have been undertaken to develop efficient and economic media, including serum- and protein-free formulations (31), generating high cell densities by using perfusion reactors instead of batch processes (32), and selection of suitable clones with higher resistance against shear stress in agitated bioreactors (14). In addition to the ready-to-use serum-free media that are already commercially available, cultivation of hybridomas is constantly improved by research activities related to specific needs. Examples are cholesterol-free media or the use of genetically engineered cell lines that are glutamine-independent, which reduces the accumulation of inhibitory substances such as ammonia (33).

The ability to produce recombinant mAb contributed to the development of chimeric mAb containing several therapeutic advantages. It is now possible to construct hete-rohybridoma cell lines where different species can contrib

Table 1. Recombinant Proteins Expressed in CHO cells






y-Glutamyl transferase (hu)

Reference enzyme for clinical tests



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