Selection of antibodies from synthetic antibody libraries

► We review selection platforms for recombinant antibody repertoires. ► We describe in vitro display systems; phage, ribosome and mRNA display. ► We describe in vivo display systems; bacterial, yeast and mammalian cells display. ► We describe how antibody libraries are constructed. ► We describe the applications of recombinant antibody repertoires. More than 2 dozen years had passed since the field of antibody engineering was established, with the first reports of bacterial [1–3] and mammalian cells [4] expression of recombinant antibody fragments, and in that time a lot of effort was dedicated to the development of efficient technological means, intended to assist in the creation of therapeutic monoclonal antibodies (mAbs). Research focus was given to two intertwined technological aspects: the selection platform and the recombinant antibody repertoires. In accordance with these areas of interest, it is the goal of this chapter to describe the various selection tools and antibody libraries existing, with emphasis on the later, and their applications. This chapter gives a far from exhaustive, subjective “historic account” of the field, describing the selection platforms, the different formats of antibody repertoires and the applications of both for selecting recombinant antibodies. Several excellent books provide detailed protocols for constructing antibody libraries and selecting antibodies from those libraries [5–13]. Such books may guide a newcomer to the field in the fine details of antibody engineering. We would like to offer advice to the novice: although seemingly simple, effective library construction and antibody isolation provide best benefits in the hands of professionals. It is an art as much as it is science.