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.
Jones
Tim D
TD
Antitope Ltd., Babraham, Cambridge, UK.
Crompton
Laura J
LJ
Carr
Frank J
FJ
Baker
Matthew P
MP
D000911:Antibodies, Monoclonal / Q000276:immunology*; D049109:Cell Proliferation; D003001:Cloning, Molecular; D018076:DNA, Complementary / Q000096:biosynthesis; D018604:Epitope Mapping; D018984:Epitopes, T-Lymphocyte / Q000276:immunology; D006801:Humans; D007114:Immunization; D007127:Immunoglobulin Constant Regions / Q000235:genetics; D008967:Molecular Biology / Q000379:methods*; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000302:isolation & purification; D017422:Sequence Analysis, DNA; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology; D014162:Transfection
D000911:Antibodies, Monoclonal; D018076:DNA, Complementary; D018984:Epitopes, T-Lymphocyte; D007127:Immunoglobulin Constant Regions; D012333:RNA, Messenger