Developing antibodies for targeting immunoglobulin and membrane-bound immunoglobulin E.
The development of anti-immunoglobulin E (IgE) antibodies for prophylactic and therapeutic applications in allergic diseases has taken nearly 20 years. Limited usage has been approved for allergic asthma. The usage in other allergic indications is in active development and may take an additional 5-10 years. The current therapeutic anti-IgE, which includes two humanized recombinant monoclonal antibodies, is the result of rational drug design, taking into consideration the structural features of IgE and membrane-bound IgE (mIgE) and various techniques collectively referred to as antibody engineering. Unlike ordinary antibodies specific for human IgE, a therapeutic anti-IgE, although capable of binding tightly to free IgE and mIgE, does not bind to IgE bound by the high-affinity IgE.Fc receptors (FcERI) on mast cells and basophils and by the low-affinity IgE.Fc receptors (FcepsilonRII, or CD23) on B cells, granulocytes, and many other cell types. The therapeutic anti-IgE is efficacious in treating allergic patients in whom IgE mediates the major allergic responses. It possesses multiple potential pharmacologic effects; researchers still are uncovering its previously unknown immunoregulatory effects. The human studies of the therapeutic anti-IgE have gradually settled many controversial views relating to IgE, such as the roles of IgE in the pathogenesis of asthma, immune defense, and early and late-phase reactions of allergic responses. Studies on the unique structural mIgE CepsilonmX domain and on the regulatory effects of anti-CepsilonmX monoclonal antibodies will be an area for future investigation of the potential of long-term IgE regulation.
Chang
Tse Wen
TW
Department of Life Science, National Tsing Hua University, Hsinchu 300, Taiwan, ROC. twchang@gate.sinica.edu.tw
D000818:Animals; D000888:Antibodies, Anti-Idiotypic / Q000494:pharmacology* / Q000627:therapeutic use; D000911:Antibodies, Monoclonal / Q000494:pharmacology* / Q000627:therapeutic use; D005544:Forecasting; D006801:Humans; D006967:Hypersensitivity / Q000276:immunology / Q000628:therapy; D007073:Immunoglobulin E / Q000276:immunology*; D007167:Immunotherapy / Q000592:standards / Q000639:trends; D011947:Receptors, Antigen, B-Cell / Q000276:immunology / Q000502:physiology; D012680:Sensitivity and Specificity; D013329:Structure-Activity Relationship
D000888:Antibodies, Anti-Idiotypic; D000911:Antibodies, Monoclonal; D011947:Receptors, Antigen, B-Cell; C026408:anti-IgE antibodies; D007073:Immunoglobulin E