Deimmunization of Monoclonal Antibodies

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


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 



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.


  1. 1.
    Morrison, S.L. (1985) Transfectomas provide novel chimeric antibodies. Science, 229, 1202–1207.PubMedCrossRefGoogle Scholar
  2. 2.
    Riechmann, L., Clark, M., Waldmann, H., and Winter, G. (1988) Reshaping human antibodies for therapy. Nature, 332, 323–327.PubMedCrossRefGoogle Scholar
  3. 3.
    Baker, M.P., and Jones, T.D. (2007) Identification and removal of immunogenicity from therapeutic proteins. Curr. Opin. Drug Discov. Devel., 10, 219.PubMedGoogle Scholar
  4. 4.
    Chester, K.A., Baker, M.P., and Mayer, A. (2005) Overcoming the immunologic response to foreign enzymes in cancer therapy. Expert Rev. Clin. Immunol., 1, 549.PubMedCrossRefGoogle Scholar
  5. 5.
    Amin, T., and Carter, G. (Nov. 2004) Immunogenicity issues with therapeutic proteins. Curr. Drug Discov., 12, 20–24.Google Scholar
  6. 6.
    Jones, T.D., Hanlon, M., Smith, B.J., Heise, C.T., Nayee, P.D., Sanders, D.A., Hamilton, A., Sweet, C., Unitt, E., Alexander, G., Lo, K.M., Gillies, S.D., Carr, F.J., and Baker, M.P. (2004) The development of a modified human IFN-alpha2b linked to the Fc portion of human IgG1 as a novel potential therapeutic for the treatment of hepatitis C virus infection. J. Interferon Cytokine Res., 24, 560–572.PubMedGoogle Scholar
  7. 7.
    Jones, T.D., Phillips, W.J., Smith, B.J., Bamford, C.A., Nayee, P.D., Baglin, T.P., Gaston, J.S.H., and Baker, M.P. (2005) Identification and removal of a promiscuous CD4+ T cell epitope from the C1 domain of factor VIII. J. Thromb. Haemost., 3, 1–10.CrossRefGoogle Scholar
  8. 8.
    De Groot, A.S., Goldberg, M., Moise, L., and Martin, W. (2006) Evolutionary deimmunization: an ancillary mechanism for self-tolerance? Cell. Immunol., 244, 148–153.PubMedCrossRefGoogle Scholar
  9. 9.
    Orlandi, R., Güssow, D.H., Jones, P.T., Winter, G. (1989) Cloning immunoglobulin variable domains for expression by the polymerase chain reaction. PNAS, 86, 3833–3837.PubMedCrossRefGoogle Scholar

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

Personalised recommendations