Deimmunization of Monoclonal Antibodies
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 wordsMonoclonal 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.
- 5.Amin, T., and Carter, G. (Nov. 2004) Immunogenicity issues with therapeutic proteins. Curr. Drug Discov., 12, 20–24.Google Scholar
- 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