Expression of Recombinant Antibodies

Frenzel, André; Hust, Michael; Schirrmann, Thomas

For the detection of different antigens, polyclonal antibodies are widely used in research and diagnostics. These sera contain a large and diverse amount of different antibodies with unknown specificities. However, polyclonal non-human antibodies may exhibit an immune response in human beings that hampers the therapeutic use for example after snake bites (12). Therefore, the production of monoclonal antibodies (mAbs) by hybridoma technology was a significant milestone (13) for the generation of antibodies for therapeutic use. As this technology is based on the fusion of antibody producing spleen cells from immunized mice or rats with immortal myeloma cell lines, its main obstacle is the inefficient immune response to highly toxic or conserved antigens. In addition, nearly all antibodies which are currently in clinical development are of human-origin or at least humanized in some aspect (9, 14, 15) to prevent immunogenicity. Consequently, Abbreviations: IgG, immunoglobulin G; mAb, monoclonal antibody. transgenic animals, especially mice, have been developed which contain a human immunoglobulin gene repertoire (16, 17) solving the problem of immunogenicity but not the need of an efficient immune response after immunization. Finally, in vitro selection technologies such as antibody phage display or ribosomal display provide a solution for the generation of human antibodies (18-22).