ABSTRACT
Large nonimmune antibody repertoires (>1011 antibodies) are now used routinely for the isolation of therapeutic antibodies since they contain high-afnity antibodies and are very diverse. Indeed, subnanomolar antibodies have been isolated directly from large nonimmune antibody libraries. These afnities are comparable with those of antibodies produced in a secondary or tertiary immune response (10−8-10−10 M) [1,2]. The size of the library is important not only for afnity but also to determine the success rate of selections against a large set of antigens [1,3]. This is well illustrated by the panel of over 1000 antibodies, all different in amino acid sequence, that was generated to the B-lymphocyte stimulator (BLyS) protein [4]. Furthermore, in some cases, antibodies with the desired characteristics have been isolated from naive antibody libraries without the need for afnity maturation. Phage display is a powerful tool for generating therapeutic drugs, as illustrated by the signicant number of human antibodies currently in clinical trials that are derived from naive antibody phage display, with many more antibodies in preclinical development.
