Immunogenicity of engineered antibodies

Administration of a therapeutic antibody can lead to an anti-antibody response (AAR). Much effort has been applied to engineering antibodies with as little as possible non-human structure to minimize such responses. Here, we review reported AAR to murine, mouse–human chimeric, and humanized antibodies. Replacement of mouse immunoglobulin constant regions with human ones effects the largest immunogenicity reduction. Humanization of variable domains effects a further decrease.