Abstract

Introduction

Preclinical Immunochemistry

Preclinical Activity

Clinical Safety and Efficacy

Conclusion

Discussion
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Development of an anti-IgE for the treatment of allergic asthma and rhinoconjunctivitis has provided novel insights to the role of IgE in allergic inflammation. Presta,etal engineered and humanized the nonanaphylactogenic rhuMAbE25 (E25)[JBC 1994;269:26368]. Preclinical E25 studies have revealed: inhibition of myogenic responses in isolated lung strips passively sensitized [Shields, Int Arch Allergy Immunol 1995; 107:308]; decr ova & parasite burden in murine schistosomiasis [JExMed 1994;180:43]; reduced granulomatous inflam in a muCepsilon KO in response to S Mansoni [King, JI 1997;158:294]. Clinical studies have shown: significant decr in late asthma responses and PC20meth [Fahy, AJRCCM 1997;155:1828]; reduced EAR @27da of treatment [Boulet, AJRCCM 1997;158:1438] decreased sputum neutrophils and MPO [Busse, AJRCCM 1998;157:A456]; down-regulation of hu basophil FcERI after 90da E25 [MacGlashan, etal JI 1997;158: 1438]; and decreased Dp/Df prick skin tests reactivity [Togias, etal JACI 1998;101:S171]. Multicenter randomized, dbl-blinded trials have shown E25 to be safe and effective in moderate to severe allergic asthma with demonstrated reductions in asthma symptoms, decr use of rescue meds, reductions in oral & inhaled corticosteroids, fall in exacerbations and improved PEFR [Zeiger,etal AnnALlergy Asthma Immunol 1998:80:80; Metzger, JAllergy Clin Immunol 1998:101:S231]. Years before E25 becomes an accepted therapy for allergic asthma, rhuMAbE25 will have taught us much about the role IgE plays in allergic inflammation [supported by Genentech, Inc, Novartis, Pharma, and Tanox Biosystems].

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Presentation Number SAfick0528
Keywords: asthma, immunoglobulin-E, inflammation, FcERI, LAR