humanized mice

We have also optimized a chain shuffling strategy that is an entirely selective humanization strategy based on construction and screening of two chimeric phage display libraries. In this approach, the light chain of the rodent antibody is first replaced by light chains in one of our well-tested human antibody libraries; the resulting hybrid antibody library is then screened by panning against the particular antigen. After that, the heavy chain of the selected hybrid antibodies is replaced by heavy chains of the human antibody library. Subsequent screening of this secondary chimeric library will produce fully humanized antibodies. Since phage display library screening mimics in vivo antibody selection and evolution procedure, chain shuffling can result in humanized antibodies whose affinities are higher than that of the original antibody. Also, this sequential chain shuffling procedure can generate several versions of humanized antibodies with different sequences. The production of multiple humanized antibodies retaining the same epitope specificity is important in therapeutic regimens that call for long-term treatment with antibodies in which anti-idiotypic responses might be avoided by administration of alternative antibodies.