HUMANIZATION OF AN ANTIBODY-DIRECTED AGAINST IGE

IgE antibodies bind to specific high-affinity receptors on mast cells, leading to mast cell degranulation and release of mediators, such as histamine, which produce symptoms associated with allergy. Hence, anti -IgE antibodies that block binding of IgE to its high-affinity recepto r are of potential therapeutic value in the treatment of allergy. Thes e antibodies must also not bind to IgE once it is bound to the recepto r because this would trigger histamine release. This study describes t he humanization of a murine antibody, MaE11, with these characteristic s. Variants of the humanized antibody were evaluated to probe the impo rtance of framework residues on antibody binding and to determine whic h charged residues in the CDR interacted with IgE. We found that only five changes in human framework residues were required to provide for binding comparable to that of the original murine antibody.