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Deimmunization of Monoclonal Antibodies

  • Tim D. Jones
  • Laura J. Crompton
  • Frank J. Carr
  • Matthew P. Baker
Protocol
Part of the Methods in Molecular Biology™ book series (MIMB, volume 525)

Abstract

Immunogenicity is a major limitation to therapy with certain monoclonal antibodies and proteins. A major driver for immunogenicity is the presence of human T-cell epitopes within the protein sequence which can activate helper T-cells resulting in the sustained production of antibodies and neutralization of the therapeutic effect. Deimmunization is a new technology for location and removal of T-cell epitopes through the combined use of immunological and molecular biology techniques. In the case of deimmunization of antibodies, mutations to remove T-cell epitopes can generally be introduced without significantly reducing the binding affinity of the antibody. Typically, “deimmunized” antibodies are created with human constant regions and by expression of genes encoding these antibodies in mammalian cells. This chapter details a method for creation of a deimmunized antibody for production in mammalian cells.

Key words

Monoclonal antibodies humanization deimmunization T-cell epitope immunogenicity PCR 

Notes

Acknowledgments

The authors would like to thank Dr Laura Perry and Dr Simon Keen for technical and editorial assistance in the development of the methods described.

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Copyright information

© Humana Press, a part of Springer Science+Business Media, LLC 2009

Authors and Affiliations

  • Tim D. Jones
    • 1
  • Laura J. Crompton
    • 1
  • Frank J. Carr
    • 1
  • Matthew P. Baker
    • 1
  1. 1.Antitope Ltd.BabrahamUK

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