Phage Display Technology as a Powerful Platform for Antibody Drug Discovery

Abstract

Antibody drugs with a high affinity and specificity are effective and safe for intractable diseases, such as cancers and autoimmune diseases. Furthermore, they have played a central role in drug discovery, currently accounting for eight of the top 20 pharmaceutical products worldwide by sales. Forty years ago, clinical trials on antibody drugs that were thought to be a magic bullet failed, partly due to the immunogenicity of monoclonal antibodies produced in mice. The recent breakthrough in antibody drugs is largely because of the contribution of phage display technology. Here, we reviewed the importance of phage display technology as a powerful platform for antibody drug discovery from various perspectives, such as the development of human monoclonal antibodies, affinity enhancement of monoclonal antibodies, and the identification of therapeutic targets for antibody drugs.

Discovery of Antivirals Using Phage Display

“…Since the discovery of hybridoma technology in 1975 [106], monoclonal antibodies (mAbs) have been important therapeutic agents because of their features, such as unique target specificity, ability to target a wide range of molecules, and long serum halflife [43,107,108]. The scientific and ethical concerns presented by antibodies derived from animal immunization made researchers investigate alternative technologies [109].…”

“…After the first description of phage display peptide libraries in 1985 by George Smith [40], the technique was used for the construction of antibody libraries by Gregory Winter and his colleagues, who pioneered the development of antibody drugs by phage display technology [41,42]. Phage display technology as well as the different phage display platforms used in drug discovery have been reviewed elsewhere and will not be further discussed herein [43][44][45]. In this review, we summarize the most common protein scaffolds used in construction of phage display libraries and their current applications in antiviral discovery.…”

Exploring protein-protein interactions at the proteome level

“…One distinct advantage of phage display is that the combinatorial search for interacting partners can be combined with multiple rounds of amplification, decreasing the noise in the technique and allowing the identification of very high-affinity binders. By enabling the detection of high-affinity antibody interactions, phage display has played an essential role in biomedical research and contributed to the fields of immunology, cell biology, drug discovery, and pharmacology (Nagano and Tsutsumi, 2021). However, there are some technical drawbacks to the approach: (1) it can be difficult and time-consuming to generate high-quality libraries for large-scale PPI screening (Caberoy et al, 2010); (2) it can have unintended effects on the folding of the displayed protein; and (3) using fusion proteins may also hinder the correct folding and binding between the interacting domains.…”

Potential Applications of Fluorescence-Activated Cell Sorting (FACS) and Droplet-Based Microfluidics in Promoting the Discovery of Specific Antibodies for Characterizations of Fish Immune Cells

“…Specifically, the hybridoma technology, fluorescencea c t i v a t i o n c e ll s o r t i n g (F A C S ) a n d dr o p le t -b a s e d microfluidics technologies with an emphasis on the latter two. Other methods, like phage display technology is not included in this review due to inherently different antibodyproducing mechanisms, and readers interested in this specific technology are referred to excellent reviews elsewhere (99,100). Our main goal is to provide alternative options for the development of mAbs in this field, which will be the basis of identifying and separating immune cell types and characterizing respective roles to further our understanding of teleost cellular immunity.…”