ABSTRACT
The unique binding specificity and affinity provided by monoclonal antibodies has resulted in a rapid expansion in the immunodiagnostic industry during the 1980s, with hybridoma technology providing straightforward selection procedures to identify specific affinity reagents against selected target molecules. However, the hybridoma approach is laborious, and the method often fails to produce affinity reagents against certain target molecules. Furthermore, the production of human antibodies has been hindered because it is not ethically acceptable to immunize human individuals to generate immunological specificity. Alternative strategies such as Epstein-Barr virus (EBV) immortalization of antibody-producing human B cells offer some advantages for the production of therapeutic antibodies but, even so, tolerance prevents the generation of self-specific antibodies. There is a distant hope for the production of human antibodies using transgenic mice in which the natural immune repertoire has been replaced by human genes. However, whilst these techniques remain in the future, we are currently witnessing a technology revolution which utilizes bacteria to display a diverse library of antibodies equivalent to the mammalian immune repertoire and thereby avoids the use of live animals. The technology is based on novel protein engineering strategies that rely on a bacterial expression system rather than a mouse for the rapid selection of antibodies (reviewed by Winter and Milstein, 1991; also Hoogenboom et al., 1991; Huse et al., 1989; Marks et al., 1991b; McCafferty et al., 1990).
