Humanizing Via A Chimeric Intermediate
The humanization process may, however, include the creation of a mouse-human chimera in an initial step (mouse Fab spliced to human Fc). Thereafter the chimera might be further humanized by the selective alteration of the sequence of amino acids in the Fab portion of the molecule. The process must be "selective" to retain the specificity for which the antibody was originally developed. That is, since the CDR portions of the Fab are essential to the ability of the antibody to bind to its intended target, the amino acids in these portions cannot be altered without the risk of undermining the purpose of the development. Aside from the CDR segments, the portions of the Fab sequence that differ from those in humans can be corrected by exchanging the appropriate individual amino acids. This is accomplished at the DNA level using mutagenesis.
Naming of humanized chimeras includes the stem for both designations (-xi- + -zu-). Otelixizumab is an example of a humanized chimera currently in clinical trials for treatment of rheumatoid arthritis and diabetes mellitus.
Read more about this topic: Humanized Antibody
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