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 (FcɛRI) on basophils and mast cells. It also does not cause activation and degranulation of IgE-pulsed, human FcɛRI-expressing rat basophilic leukemic cells (RBL SX-38). The mAb can inhibit IgE binding to recombinant α chain of human FcɛRI in ELISA and to human FcɛRI-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 (FcɛRII, 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.
Institute of Bioinformatics and Structural Biology, National Tsing Hua University, Hsinchu, Taiwan.
Yu-Yu
YY
Shiung
Chen-Yi
CY
Chiang
Jiun-Bo
JB
Chen
Pheidias C
PC
Wu
Alfur Fu-Hsin
AF
Hung
Donic Chien-Sheng
DC
Lu
Rong-Long
RL
Pan
Tse Wen
TW
Chang
D000818:Animals; D000888:Antibodies, Anti-Idiotypic / Q000276:immunology* / Q000378:metabolism / Q000494:pharmacology; D000911:Antibodies, Monoclonal / Q000276:immunology* / Q000378:metabolism / Q000494:pharmacology; D061067:Antibodies, Monoclonal, Humanized / Q000276:immunology / Q000378:metabolism / Q000494:pharmacology; D000918:Antibody Specificity; D001402:B-Lymphocytes / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D001491:Basophils / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D001667:Binding, Competitive; D004797:Enzyme-Linked Immunosorbent Assay; D000939:Epitopes; D006801:Humans; D006969:Hypersensitivity, Immediate / Q000188:drug therapy / Q000276:immunology* / Q000378:metabolism; D007073:Immunoglobulin E / Q000276:immunology* / Q000378:metabolism; D008407:Mast Cells / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D000069444:Omalizumab; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D051381:Rats; D017455:Receptors, IgE / Q000276:immunology* / Q000378:metabolism
D000888:Antibodies, Anti-Idiotypic; D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000939:Epitopes; D017455:Receptors, IgE; C026408:anti-IgE antibodies; D000069444:Omalizumab; D007073:Immunoglobulin E