Anti-IgE as a mast cell-stabilizing therapeutic agent

After nearly 20 years of development, humanized monoclonal anti-IgE antibodies have been shown in about 20 phase II and III clinical trials to be effective and safe in treating allergic asthma, perennial and seasonal allergic rhinitis, and allergic reactions to peanuts. Omalizumab has been approved in the United States, European Union, and several other countries for treating patients 12 years and older with moderate-to-severe allergic asthma. Although anti-IgE is often referred to as an IgE-neutralizing antibody and can block IgE's binding to high-affinity IgE Fc receptors (FcepsilonRI) on mast cells and basophils, it has multiple immunoregulatory effects. One such effect is that as the result of depleting free IgE, FcepsilonRI on mast cells and basophils is downregulated to less than 5% within a few weeks to a few months of anti-IgE treatment. This renders the mediator-packed inflammatory cells insensitive to allergen stimulation. Hence this therapeutic anti-IgE represents a new class of mast cell-stabilizing agents, reducing FcepsilonRI density on mast cells and basophils and causing them to be insensitive to allergens. This mechanism contrasts with that of cromones, mast cell-stabilizing agents that retard Ca++ mobilization and the degranulation process, thus deflating the intracellular activation signal triggered by IgE-FcepsilonRI aggregation.