For example, human chimeric antibodies were produced by replacing the Fc sequence of mouse antibodies with that of human antibodies to reduce immunogenicity. This problem has been overcome by antibody engineering. However, clinical trials have largely failed because mouse monoclonal antibodies recognized as heterologous proteins in the human body are highly immunogenic, and they showed reduced efficacy because of human anti-mouse antibodies, so-called HAMAs. Since this discovery, monoclonal antibodies with high specificity and affinity to target molecules were expected to be used as magic bullets for various clinical applications. In 1975, Köhler and Milsterin established a method for generating monoclonal antibodies using hybridomas. Development of Antibody Drugs Using Phage Display Technology More than 70 phage-derived monoclonal antibodies have entered clinical studies, and 14 of them have been approved for use till May 2020.Ģ. Therefore, the phage display technology allows the construction of various phage antibody libraries such as naïve, immunized and synthetic phage antibody and contributes to the current development of antibody drugs. Subsequently, several antibody formats, such as scFv, fragment antigen-binding (Fab), and variable fragment (VHH) derived from heavy chain antibodies of Camelidae, have been reported to be displayed on the phages ( Figure 1). displayed a single-chain variable fragment (scFv) antibody that consists of the variable heavy chain (VH) and the variable light chain (VL) joined together by a flexible peptide linker in 1990. In particular, phage display technology has become a powerful platform for drug discovery in life science because it is easy to produce antibodies in vitro. Although various kinds of molecular display technologies such as ribosome display, and yeast display technologies have been proposed, phage display technology is frequently employed because of a high diversity of molecules that can be displayed and ease of handling. Therefore, the development of phage display technology provides optimal sequences to target peptides or proteins, unlike conventional alanine scanning and other methods, and aids understanding of their molecular evolution. Therefore, the clones with an affinity for the target of interest or those with the ability to migrate to the target tissue are enriched from the library. Phage display technology allows the construction of libraries in which various peptides and proteins are displayed on the phages, and then the most suitable clone is selected from the library by in vitro panning. demonstrated phage display technology using artificial peptide sequences on the N-terminus of a bacteriophage surface protein.
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