Antibodies From Diversity Libraries and Display Technologies

The pharmaceutical industry discovers small molecule drugs by screening very large compound libraries to obtain lead ‘hits’ with affinities in the micromolar range. The tools of medicinal chemistry are then applied to these leads to improve their binding to the drug target, resulting in a new drug entity. In the late 1980s, advances in molecular biology made it possible to apply the same type of strategy to the discovery of fully human antibodies. Libraries of millions to billions of different antibodies could be generated and methods were developed that allowed the isolation of rare lead antibodies binding to a specific target antigen. As with the medicinal chemists, similar methods could be applied to diversify the structure of lead antibodies and allow the selection of antibodies with considerably higher affinities. The methods used to create such libraries are called display technologies and include phage display, yeast display, ribosome display and a number of other less frequently used technologies. Display technologies have three characteristics in common:

(1) a method for generating antibody gene  diversity

(2) a method for linking the antibody genotype with the expressed antibody phenotype; and

(3) a method for isolating rare antigen binding antibodies (and their genes) from a majority of nonbinding antibodies.