IgE inhibition as a therapy for allergic disease

Abstract

Monoclonal antibodies are potentially useful therapeutic agents in a variety of immunologically mediated diseases, since they offer the theoretical advantage of selectively targeting the mediators of the immuno-pathogenesis. It has been well established that IgE antibody synthesized by the immune system plays a pivotal role in the cascade of biochemical events leading to the allergic reaction. The aim of these studies was to eliminate IgE with a monoclonal antibody as the approach for treatment of atopic disease. To this end, a murine monoclonal antibody (MAE11) directed against IgE was identified which had all of the properties necessary to interfere with IgE responses. To avoid the problems of antigenicity associated with chronic administration of murine antibodies MAE11 was humanized. The best of several humanized variants, version 25 (rhuMAb-E25), was selected for clinical trials in allergic asthma and seasonal allergic rhinitis. In a series of phase I safety studies, rhuMAb-E25, by single or multidose administrations, was shown to be very well tolerated. Phase II studies were then designed to determine whether elimination of serum IgE, as a result of rhuMAb-E25 administration, had a significant impact on allergic symptoms. Results of these clinical trials establish the involvement of IgE in the pathophysiology of rhinitis and asthma and suggest a novel treatment for allergic disease.