Humanization by Resurfacing

Monoclonal antibodies can be humanized by changing murine framework surface residues into those that are typically observed in closely related human counterparts. This technique of resurfacing an antibody is based on the observation that the antigenicity of a protein is determined by the accessible and protruding residues. Since nothing is changed to the CDR-framework interactions at the interior, and only subtle changes are made to the exterior, this usually has only minor effects on the conformation and the activity of the resurfaced antibody. A detailed structure-based protocol is proposed. The approach has been successfully applied to two independent antibodies.