Use of human germline genes in a CDR homology-based approach to antibody humanization.
We report a new method of humanizing antibodies by complementarity determining region (CDR) grafting. Our method differs from others in that we choose human framework sequences from the set of human germline genes based on the structural similarity of the human CDRs to those of the mouse antibody to be humanized. The structural similarity is evaluated by scoring residue-to-residue homology of the mouse CDRs to human candidates with the same Chothia canonical structures. The method is illustrated with the humanization of the anti-lysozyme antibody D1.3.
Hwang
William Ying Khee
WY
Division of Human Biology, Fred Hutchinson Cancer Research Center, 1100 Fairview Avenue, C3-168, Seattle, WA 98109-1024, USA.
Almagro
Juan Carlos
JC
Buss
Timothy N
TN
Tan
Philip
P
Foote
Jefferson
J
D000595:Amino Acid Sequence; D000818:Animals; D000911:Antibodies, Monoclonal / Q000235:genetics* / Q000276:immunology; D022801:Complementarity Determining Regions / Q000737:chemistry / Q000235:genetics* / Q000276:immunology; D004926:Escherichia coli / Q000235:genetics; D005803:Genes, Immunoglobulin; D005854:Germ Cells / Q000502:physiology; D006801:Humans; D007143:Immunoglobulin Heavy Chains / Q000235:genetics / Q000378:metabolism; D007147:Immunoglobulin Light Chains / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000737:chemistry; D015202:Protein Engineering / Q000379:methods*; D017386:Sequence Homology, Amino Acid
D000911:Antibodies, Monoclonal; D022801:Complementarity Determining Regions; D007143:Immunoglobulin Heavy Chains; D007147:Immunoglobulin Light Chains; D010446:Peptide Fragments