Evolution of phage display libraries for therapeutic antibody discovery

ABSTRACT

Monoclonal antibodies (mAbs) and their derivatives have emerged as one of the most important classes of biotherapeutics in recent decades. The success of mAb is due to their high versatility, high target specificity, excellent clinical safety profile, and efficacy. Antibody discovery, the most upstream stage of the antibody development pipeline, plays a pivotal role in determination of the clinical outcome of an mAb product. Phage display technology, originally developed for peptide directed evolution, has been extensively applied to discovery of fully human antibodies due to its unprecedented advantages. The value of phage display technology has been proven by a number of approved mAbs, including several top-selling mAb drugs, derived from the technology. Since antibody phage display was first established over 30 years ago, phage display platforms have been developed to generate mAbs targeting difficult-to-target antigens and tackle the drawbacks present in in vivo antibody discovery approaches. More recently, the new generation of phage display libraries have been optimized for discovery of mAbs with ”drug-like” properties. This review will summarize the principles of antibody phage display and design of three generations of antibody phage display libraries.

KEYWORDS:

• Antibody developability
• antibody selection
• library design
• phage display
• therapeutic antibody discovery

Acknowledgments

The author gratefully acknowledges Frederic Fellouse (Abtech Therapeutics SAS, Marseille, France) who kindly proofread the manuscript and provided his insights, as well as useful comments and suggestions. The author also thanks Peter Meinke and Nora Kostow (Tri-Institutional Therapeutics Discovery Institute, New York, United States) for providing helpful comments.

Disclosure statement

No potential conflict of interest was reported by the author.

Correction Statement

This article has been corrected with minor changes. These changes do not impact the academic content of the article.

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Funding

The author(s) reported there is no funding associated with the work featured in this article.