Phage display antibody repertoire8/3/2023 Due to the completely in vitro selection system, phage display surpasses in vivo discovery approaches by enabling the discovery of antibodies against virtually any targets or epitopes, including those that are either toxic or nonimmunogenic for animal immunization. As the other approach, phage display technology has greatly advanced the therapeutic mAb discovery process by providing a highly versatile approach and overcoming many drawbacks present in in vivo antibody generation technologies. In addition, because the selection is entirely completed in vivo, there is limited control over properties, such as specificity and epitope. However, this process is time intensive and requires the antigen to be immunogenic and nontoxic. Antibodies with high affinity and developability are selected during the development of immune response. For in vivo animal immunization, antibodies are generated through repeated immunization of target of interest. 2 To date, approved fully human therapeutic antibodies were discovered from either in vivo animal immunization (including humanized mice and convalescent human donors) or in vitro phage display technology. 2, 3 The global mAb market size reached ~$150 billion in 2020 and is expected to double in the next five years. Monoclonal antibodies (mAbs) and their derivatives 1 represent a major class of therapeutics and have become the best-selling drugs in United States in recent years. This review will summarize the principles of antibody phage display and design of three generations of antibody phage display libraries. More recently, the new generation of phage display libraries have been optimized for discovery of mAbs with ”drug-like” properties. 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. 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. Phage display technology, originally developed for peptide directed evolution, has been extensively applied to discovery of fully human antibodies due to its unprecedented advantages. 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. The success of mAb is due to their high versatility, high target specificity, excellent clinical safety profile, and efficacy. Monoclonal antibodies (mAbs) and their derivatives have emerged as one of the most important classes of biotherapeutics in recent decades.
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