Tse Wen Chang

Genomics Research Center, Academia Sinica, Taiwan

Abstract:

Two types of antibodies are being developed to target soluble IgE in the blood and membrane-bound IgE (mIgE) on IgE-expressing B lymphoblast and memory B cells, for treating allergy and asthma. An ordinary anti-IgE antibody, if were injected into a person, would most likely cause massive activation of mast cells and basophils and probably anaphylactic shocks. Both types of the antibodies being developed to target the IgE pathway can avoid this deadly effect of an ordinary anti-IgE antibody. The therapeutic anti-IgE antibody, omalizumab (trade name Xolair), binds to an epitope on the CH3 domain of IgE near the binding site for the high-affinity IgE.Fc receptor. More than 100 corporate-sponsored clinical trials on Xolair have been or are being carried out and have shown it to be effective and safe for treating various allergic diseases and IgE-mediated diseases. Xolair has been approved in many countries for treating severe, persistent allergic asthma, uncontrollable with high doses of corticosteroids. The second type of antibodies targets the CemX domain, a discrete segment of 52 a.a. residues, located between the CH4 domain and the C-terminal membrane-anchor peptide of mIgE. The results of a Phase IIa trial have shown that an anti-CemX antibody can block the new synthesis of IgE and hence mitigate the effects of antigen stimulation. This presentation will provide updates on the development of these two types of antibodies, which target the IgE pathway.