Arrayed antibody library technology for therapeutic biologic discovery

• Published in: Methods (San Diego, Calif.) Vol. 60; no. 1; pp. 91 - 98
• Main Authors: Bentley, Cornelia A., Bazirgan, Omar A., Graziano, James J., Holmes, Evan M., Smider, Vaughn V.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 15.03.2013
• Subjects: Antibodies; Antibody; Arrayed protein library; Biological Products - chemical synthesis; Biological Products - chemistry; Drug Discovery; Flow Cytometry; Peptide Library; Protein Engineering; Screening high-throughput flow cytometry; Spatially addressed library; LIMS; Protein engineering; Screening high-throughput flow cytometry; D; IMAC; SAR; Antibody; Fab; MHC; J; FACS; CVB; mAb; CDR; V; Arrayed protein library; GPCR; Spatially addressed library; BLAST
• ISSN: 1046-2023; 1095-9130
• DOI: 10.1016/j.ymeth.2013.02.003

Traditional immunization and display antibody discovery methods rely on competitive selection amongst a pool of antibodies to identify a lead. While this approach has led to many successful therapeutic antibodies, targets have been limited to proteins which are easily purified. In addition, selection driven discovery has produced a narrow range of antibody functionalities focused on high affinity antagonism. We review the current progress in developing arrayed protein libraries for screening-based, rather than selection-based, discovery. These single molecule per microtiter well libraries have been screened in multiplex formats against both purified antigens and directly against targets expressed on the cell surface. This facilitates the discovery of antibodies against therapeutically interesting targets (GPCRs, ion channels, and other multispanning membrane proteins) and epitopes that have been considered poorly accessible to conventional discovery methods.