Anti-IgE as novel therapy for the treatment of asthma.
Immunoglobulin-E (IgE) is believed to be the central effector antibody reacting to allergen in patients with allergic asthma. Clinical manifestations of allergic asthma result from the release of chemical mediators from mast cells and basophils on exposure to allergen. A humanized murine monoclonal antibody to IgE, rhuMAb-E25, recognizes the specific Fc epsilon3 portion of circulating IgE that binds to the high-affinity IgE receptor, Fc epsilonRI. In clinical studies, single and multiple doses of subcutaneous and intravenous rhuMAb-E25 have been shown to reproducibly reduce the serum free IgE concentrations in a dose-dependent manner. Clinical trials conducted in aeroallergen bronchoprovocation laboratories demonstrated that decreasing circulating IgE resulted in significant attenuation of the early and late asthmatic responses. Studies completed in moderate to severe allergic asthmatics have extended the safety and efficacy of rhuMAb-E25. Significant improvements in asthma symptoms, meaningful reductions in corticosteroid agents while decreasing reliance on bronchodilator rescue drugs, decreased asthma exacerbations, and improved quality of life have been documented. Because of the remarkable protein engineering and the humanization technology now available, rhuMAb-E25 therapy has elicited no antibody responses and has been safely administered to atopic subjects. rhuMAb-E25 as a novel monoclonal antibody, the first to be applied to lung diseases, holds promise for the control of many IgE-mediated diseases.
Fick
R B
RB
Clinical Sciences, Genetech, Inc., South San Francisco, CA 94080-4990, USA.
D000485:Allergens / Q000627:therapeutic use*; D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D001249:Asthma / Q000628:therapy*; D002648:Child; D002986:Clinical Trials as Topic; D006801:Humans; D007073:Immunoglobulin E / Q000276:immunology*; D051379:Mice
D000485:Allergens; D000911:Antibodies, Monoclonal; C401983:rhuMAb-E25; D007073:Immunoglobulin E