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Beyond natural antibodies: the power of in vitro display technologies

Nature Biotechnology volume 29, pages 245–254 (2011)Cite this article

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Abstract

In vitro display technologies, best exemplified by phage and yeast display, were first described for the selection of antibodies some 20 years ago. Since then, many antibodies have been selected and improved upon using these methods. Although it is not widely recognized, many of the antibodies derived using in vitro display methods have properties that would be extremely difficult, if not impossible, to obtain by immunizing animals. The first antibodies derived using in vitro display methods are now in the clinic, with many more waiting in the wings. Unlike immunization, in vitro display permits the use of defined selection conditions and provides immediate availability of the sequence encoding the antibody. The amenability of in vitro display to high-throughput applications broadens the prospects for their wider use in basic and applied research.

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Figure 1: The unique capabilities of in vitro selection offer advantages over the immunization of animals for antibody generation.
Figure 2: In vitro selected antibodies can recognize minute differences in small molecules.
Figure 3: Mechanisms for blocking or activating receptor signaling using antibodies.
Figure 4: An engineered dual specificity synthetic Fab.

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Acknowledgements

A.R.M.B. is grateful to the US National Institutes of Health (P50GM085273 and R01-HG004852-01A1), US Department of Energy (GTL program) and the US Department of Defense, Defense Threat Reduction Agency for funding. S.D. gratefully acknowledges funding by the EU 7th framework programme (Projects: Affinomics and AffinityProteome). J.M. is pleased to acknowledge funding by the Wellcome Trust.

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Authors and Affiliations

  1. Los Alamos National Laboratory, Los Alamos, New Mexico, USA

    Andrew R M Bradbury

  2. University of Toronto, Toronto, Ontario, Canada

    Sachdev Sidhu

  3. Technical University Braunschweig, Braunschweig, Germany

    Stefan Dübel

  4. University of Cambridge, Cambridge, UK

    John McCafferty

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Bradbury, A., Sidhu, S., Dübel, S. et al. Beyond natural antibodies: the power of in vitro display technologies. Nat Biotechnol 29, 245–254 (2011). https://doi.org/10.1038/nbt.1791

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