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Selecting and screening recombinant antibody libraries

Abstract

During the past decade several display methods and other library screening techniques have been developed for isolating monoclonal antibodies (mAbs) from large collections of recombinant antibody fragments. These technologies are now widely exploited to build human antibodies with high affinity and specificity. Clever antibody library designs and selection concepts are now able to identify mAb leads with virtually any specificity. Innovative strategies enable directed evolution of binding sites with ultra-high affinity, high stability and increased potency, sometimes to a level that cannot be achieved by immunization. Automation of the technology is making it possible to identify hundreds of different antibody leads to a single therapeutic target. With the first antibody of this new generation, adalimumab (Humira, a human IgG1 specific for human tumor necrosis factor (TNF)), already approved for therapy and with many more in clinical trials, these recombinant antibody technologies will provide a solid basis for the discovery of antibody-based biopharmaceuticals, diagnostics and research reagents for decades to come.

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Figure 1: Generating binding site diversity in the immune system.

Katie Ris

Figure 2: Creating and selecting recombinant antibody libraries.

Katie Ris

Figure 3: Methods for in vitro selection for binding.

Katie Ris

Figure 4: Binding-site diversity in recombinant antibody libraries.

Katie Ris

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Acknowledgements

I thank many colleagues including Jane Osbourn and Lutz Jermutus, Clive Wood, Zhenping Zhu, Patrick Bauerle, Herren Wu, David Chen and Lex Bakker for sharing unpublished results and am grateful to Mark Alfenito for reviewing the manuscript.

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Hoogenboom, H. Selecting and screening recombinant antibody libraries. Nat Biotechnol 23, 1105–1116 (2005). https://doi.org/10.1038/nbt1126

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