Allergen, IgE and mast-cell-directed therapies: An overview

In addition to traditional drug development strategies, a number of current approaches focus on modulation of the immune response to allergens or, the allergens themselves. Disease-modulating specific immunotherapy has been u sed for many years and has been shown to be efficacious, although this form of treatment is slow and carries the risk of systemic adverse reactions. T he identification of naturally occurring allergen isoforms of the native pr otein which do not bind IgE has led to modification of a number of allergen s by site-directed mutagenesis. Such proteins have a reduced or absent inte raction with IgE whilst retaining much of their ability to stimulate T cell s. The improved safety profile of such molecules may result in larger, more efficacious doses of protein being given with improved safety. Fragments o f allergen molecules, such as peptides, are also under development, employi ng a similar rationale of destroying IgE binding epitopes whilst retaining T cell determinants. Neutralization of specific molecules in the inflammato ry cascade is currently being addressed with 'humanized' monoclonal antibod ies and soluble receptors/ receptor antagonists, directed towards IgE, cyto kines such as IL-4 and IL-5, and cell surface molecules such as CD23.