Abstract
Phage display technology has played a key role in the remarkable progress of discovering and optimizing antibodies for diverse applications, particularly antibody-based drugs. This technology was initially developed by George Smith in the mid-1980s and applied by John McCafferty and Gregory Winter to antibody engineering at the beginning of 1990s. Here, we compare nine phage display antibody libraries published in the last decade, which represent the state of the art in the discovery and development of therapeutic antibodies using phage display. We first discuss the quality of the libraries and the diverse types of antibody repertoires used as substrates to build the libraries, i.e., naïve, synthetic, and semisynthetic. Second, we review the performance of the libraries in terms of the number of positive clones per panning, hit rate, affinity, and developability of the selected antibodies. Finally, we highlight current opportunities and challenges pertaining to phage display platforms and related display technologies.
Highlights
The phage display methodology has revolutionized the protein engineering field, with a major impact on antibody engineering
Only a very small fraction of this universe of 1078 unique antibody variants can be sampled in a phage display antibody library
We reviewed nine of the libraries generated over the last decade
Summary
The phage display methodology has revolutionized the protein engineering field, with a major impact on antibody engineering. In the last decade it has been learned that in addition to the specificity and affinity, other properties account for the success of a therapeutic antibody in Antibodies 2019, 8, 44 clinical trials Such properties, collectively called developability [18,19], include (but are not limited to) cross-reactivity against the human target and orthologs from relevant tox species and animal models, solubility, expression yield in manufacturing cells, and thermal and long-term stability. Collectively called developability [18,19], include (but are not limited to) cross-reactivity against the human target and orthologs from relevant tox species and animal models, solubility, expression yield in manufacturing cells, and thermal and long-term stability Since these properties are encoded in the amino acid sequence of the antibody, there has been a strong demand to generate phage display antibody libraries that enable the selection of highly specific and high affinity antibodies, and those that are more developable.
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