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Anti-lgE

In the late 1990s there was a very interesting drug development plan by Genentech to investigate the possibility of using inhaled anti-IgE to treat asthma. The rationale was that there was evidence for both local and systemic effects of IgE in the etiology of asthma. The hypothesis was that local delivery of anti-IgE to the lung would inhibit IgE-mediated inflammation in the lung and provide improved asthma therapy. Both nonclinical [37] and clinical studies [38] were undertaken. The definitive data from the clinical trials showed that inhaled anti-IgE were well tolerated. It was concluded “that aerosol administration of an anti-IgE monoclonal antibody does not inhibit the airway responses to inhaled allergen in allergic asthmatic subjects.” The nonclinical studies had demonstrated that aerosol delivery did result in good deposition of the anti-IgE in lungs. It was also found that only <0.1% of the IgE delivered to lungs was absorbed into blood. These data confirm that local deposition was indeed achieved and the low absorption into blood, consistent with the high molecular weight of anti- IgE, suggested a potential long-term residence in lung. In this case, systemic delivery of anti-IgE by subcutaneous injection produces superior therapeutic results for treating asthma than local delivery by inhaled administration.

The results of this program suggest that for new initiatives with inhaled antibodies, there needs to be careful consideration of target receptors, receptor affinities, and relative influence of systemic and local effects. Although not discussing inhaled therapies, Catley et al. [39] have reviewed potential use of monoclonal antibodies to treat asthma. There has been some conjecture that future targets with relatively high- affinity receptors in the lung and high lung specificity might be attractive opportunities. Another factor supporting inhaled use for future therapies would be if there were no systemic delivery alternative for the proposed therapy or if the only systemic therapy is intravenous delivery.

 
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