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The Antibody Humanization Process by CDR Grafting

The transfer of antigen binding loops from a non-human antibody donor to a human framework must be performed so that the native loop conformations are retained for binding. Often, antigen binding affinity is greatly reduced or abolished after CDR grafting. This binding activity is only restored after reverting one or more human framework residues to donor equivalents in the humanized antibody. The identification of critical framework residues that contribute to CDR conformation represents the most difficult and unpredictable step in the antibody humanization process. Here antibody modeling procedures and sequence analysis are described to assist the selection of framework mutations in the antibody humanization process.

Leonardo Borras, Head, Protein Engineering, ESBATech LLC

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