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BioDrugs

, Volume 32, Issue 4, pp 339–355 | Cite as

Therapeutic Monoclonal Antibodies to Complex Membrane Protein Targets: Antigen Generation and Antibody Discovery Strategies

  • Roger B. Dodd
  • Trevor Wilkinson
  • Darren J. Schofield
Review Article

Abstract

Cell surface membrane proteins comprise a wide array of structurally and functionally diverse proteins involved in a variety of important physiological and homeostatic processes. Complex integral membrane proteins, which are embedded in the lipid bilayer by multiple transmembrane-spanning helices, are represented by families of proteins that are important target classes for drug discovery. Such protein families include G-protein-coupled receptors, ion channels and transporters. Although these targets have typically been the domain of small-molecule drugs, the exquisite specificity of monoclonal antibodies offers a significant opportunity to selectively modulate these target proteins. Nevertheless, the isolation of antibodies with desired pharmacological functions has proved difficult because of technical challenges in preparing membrane protein antigens for antibody drug discovery. In this review, we describe recent progress in defining strategies for the generation of membrane protein antigens. We also describe antibody-isolation strategies that identify antibodies that bind the membrane protein and modulate protein function.

Notes

Compliance with Ethical Standards

Conflict of interest

Roger Dodd, Trevor Wilkinson, and Darren Schofield are full-time employees of MedImmune Ltd (UK), a company generating therapeutic antibodies to complex membrane protein targets for the treatment of a variety of diseases.

Funding

No sources of funding were used to support the writing of this review.

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Copyright information

© Springer International Publishing AG, part of Springer Nature 2018

Authors and Affiliations

  • Roger B. Dodd
    • 1
  • Trevor Wilkinson
    • 1
  • Darren J. Schofield
    • 1
  1. 1.Department of Antibody Discovery and Protein EngineeringMedImmune LtdCambridgeUK

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