Construction, function and immunogenicity of recombinant monoclonal antibodies

Much of the interest in chimaeric antibodies stems from their presumed lack of immunogenicity in humans. We have tested this assumption using mouse models and have concluded that whilst chimaerisation can certainly lead to a reduction in the total anti-antibody response, a substantial anti-variable region response can nevertheless remain. As it therefore seems likely that determinants within the variable region lead to this anti-antibody response, we have initiated experiments to test whether it might be possible to use transgenic mice that carry human immunoglobulin gene segments in their germline configuration as a means of making a repertoire of entirely human antibodies.