Humanization of an antibody directed against IgE.

TLDR

IgE binds high‑affinity receptors on mast cells, triggering degranulation and histamine release, so anti‑IgE antibodies that block this interaction are therapeutic but must not bind IgE already bound to the receptor to avoid triggering histamine release. The study reports humanizing the murine anti‑IgE antibody MaE11 to retain its receptor‑blocking properties while avoiding binding to IgE already bound to the receptor. The authors generated humanized variants and assessed how framework residues and CDR charged residues affect IgE binding. Only five framework substitutions were needed to achieve binding comparable to the original murine antibody.

Abstract

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 receptor are of potential therapeutic value in the treatment of allergy. These antibodies must also not bind to IgE once it is bound to the receptor because this would trigger histamine release. This study describes the humanization of a murine antibody, MaE11, with these characteristics. Variants of the humanized antibody were evaluated to probe the importance of framework residues on antibody binding and to determine which 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.