title: The role of phage display in therapeutic antibody discovery.
abstract: Phage display involves the expression of selected proteins on the surface of filamentous phage through fusion with phage coat protein, with the genetic sequence packaged within, linking phenotype to genotype selection. When combined with antibody libraries, phage display allows for rapid in vitro selection of antigen-specific antibodies and recovery of their corresponding coding sequence. Large non-immune and synthetic human libraries have been constructed as well as smaller immune libraries based on capturing a single individual's immune repertoire. This completely in vitro process allows for isolation of antibodies against poorly immunogenic targets as well as those that cannot be obtained by animal immunization, thus further expanding the utility of the approach. Phage antibody display represents the first developed methodology for high throughput screening for human therapeutic antibody candidates. Recently, other methods have been developed for generation of fully human therapeutic antibodies, such as single B-cell screening, next-generation genome sequencing and transgenic mice with human germline B-cell genes. While each of these have their particular advantages, phage display has remained a key methodology for human antibody discovery due its in vitro process. Here, we review the continuing role of this technique alongside other developing technologies for therapeutic antibody discovery.
authors.affiliation: Biological Defence Program, Defense Medical and Environmental Research Institute, DSO National Laboratories, 27 Medical Drive, Singapore 117510, Singapore.
authors.forename: Conrad E Z
authors.initials: CE
authors.lastname: Chan
authors.affiliation: Biological Defence Program, Defense Medical and Environmental Research Institute, DSO National Laboratories, 27 Medical Drive, Singapore 117510, Singapore.
authors.forename: Angeline P C
authors.initials: AP
authors.lastname: Lim
authors.affiliation: Department of Microbiology, Yong Loo Lin School of Medicine, National University of Singapore, 5 Science Drive 2, Singapore 117545, Singapore Immunology Program, Centre for Life Sciences, National University of Singapore, 28 Medical Drive, Singapore 117456, Singapore.
authors.forename: Paul A
authors.initials: PA
authors.lastname: MacAry
authors.affiliation: Biological Defence Program, Defense Medical and Environmental Research Institute, DSO National Laboratories, 27 Medical Drive, Singapore 117510, Singapore Department of Microbiology, Yong Loo Lin School of Medicine, National University of Singapore, 5 Science Drive 2, Singapore 117545, Singapore hbrendon@dso.org.sg.
authors.forename: Brendon J
authors.initials: BJ
authors.lastname: Hanson
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000235:genetics / Q000276:immunology / Q000627:therapeutic use; D061067:Antibodies, Monoclonal, Humanized / Q000235:genetics / Q000276:immunology / Q000627:therapeutic use; D001324:Autoantigens / Q000276:immunology; D001709:Biotechnology; D002241:Carbohydrates / Q000276:immunology; D061505:Cell Surface Display Techniques; D055808:Drug Discovery; D004353:Drug Evaluation, Preclinical; D006801:Humans; D008055:Lipids / Q000276:immunology; D019151:Peptide Library; D011506:Proteins / Q000276:immunology / Q000378:metabolism
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D001324:Autoantigens; D002241:Carbohydrates; D008055:Lipids; D019151:Peptide Library; D011506:Proteins
keywords: phage display; therapeutic antibodies