From rodent reagents to human therapeutics using antibody guided selection.
Guided selection is a method of producing a human version of a rodent or any other non-human antibody. The process is a serial transition from rodent to human via rodent-human chimaerics, through to a panel of human antibodies with similar characteristics to those of the starting rodent antibody. The guided selection process can be undertaken using either phage display or ribosome display, and chimaeric antibodies can be made either in series or parallel, with or without the retention of the original rodent CDR3s. Guided selection has successfully been used for the generation of a number of human versions of rodent antibodies, including HUMIRA, an inhibitor of tumour necrosis factor-alpha which is approved for the treatment of moderate to severe rheumatoid arthritis in over 40 countries.
Osbourn
Jane
J
Cambridge Antibody Technology, Milstein Building, Granta Park, Cambridge, CB1 6GH, UK. jane.osbourn@cambridgeantibody.com
Groves
Maria
M
Vaughan
Tristan
T
D000068879:Adalimumab; D000818:Animals; D000911:Antibodies, Monoclonal / Q000235:genetics* / Q000276:immunology / Q000627:therapeutic use; D061067:Antibodies, Monoclonal, Humanized; D020650:Combinatorial Chemistry Techniques; D006801:Humans; D007135:Immunoglobulin Variable Region / Q000235:genetics; D007202:Indicators and Reagents; D019151:Peptide Library; D015202:Protein Engineering / Q000379:methods*; D011993:Recombinant Fusion Proteins / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology; D012270:Ribosomes / Q000276:immunology / Q000378:metabolism; D012377:Rodentia / Q000276:immunology
D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D007135:Immunoglobulin Variable Region; D007202:Indicators and Reagents; D019151:Peptide Library; D011993:Recombinant Fusion Proteins; D000068879:Adalimumab