CDR Repair: A Novel Approach to Antibody Humanization

Abstract

Hybridoma technology has enabled the rapid production of a large number of monoclonal antibodies with interesting biological properties. Their use in a therapeutic setting, however, can lead to the generation of a human anti-mouse antibody (HAMA) response in patients despite the high degree of sequence similarity shared between human and mouse antibodies. This has prompted efforts to make hybridoma antibodies appear more human through the construction of chimeras, (Morrison et al. 1984) and through a process known as antibody humanization (Riechmann et al. 1988; Verhoeyen et al. 1988). The modular nature of antibodies makes the swapping of domains a relatively simple process. A chimera consisting of the mouse variable heavy (VH) and variable light (VL) domains recombinantly fused to human heavy and light constant domains is a simple way to reduce HAMA response. Yet, despite 60–75% homology to human, murine variable domains may still elicit a HAMA response.