An anti-IgE monoclonal antibody that binds to IgE on CD23 but not on high-affinity IgE.Fc receptors

A new monoclonal antibody (mAb), specific for human IgE, the central mediator of immediate-type hypersensitivity reactions, has been shown to possess a unique set of binding specificities. The mAb, 8D6, binds to a conformational epitope on the CH3 domain of human e immunoglobulin and can compete with omalizumab for binding to IgE. Like omalizumab, it does not bind to IgE bound by the high-affinity IgE.Fc receptor (Fc epsilon RI) on basophils and mast cells. It also does not cause activation and degranulation of IgE-pulsed, human Fc epsilon RI-expressing rat basophilic leukemic cells (RBL SX-38). The mAb can inhibit IgE binding to recombinant alpha chain of human Fc epsilon RI in ELISA and to human Fc epsilon RI-expressing RBL SX38 cells in fluorescence flow cytometric analysis. However, unlike omalizumab, 8D6 can bind to IgE already bound by the low-affinity IgE.Fc receptors (Fc epsilon RII, or CD23), as revealed in ELISA with recombinant CD23 and in flow cytometric analysis with human B cells. Since earlier investigators have shown that anti-CD23 mAbs can inhibit the synthesis of IgE in lymphocyte culture in vitro and can down-regulate IgE production in treated patients, 8D6 may offer pharmacological mechanisms in addition to those mediated by omalizumab, for controlling IgE in patients with allergic diseases. (C) 2011 Elsevier GmbH. All rights reserved.