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Invited Symposium: Novel Cellular and Molecular Mechanisms in Allergic Inflammation






Abstract

Introduction

Preclinical Immunochemistry

Preclinical Activity

Clinical Safety and Efficacy

Conclusion




Discussion
Board

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Anti-IgE as a Probe to Understand Allergic Inflammantion.

Fick, R.B. (Clinical Sciences, Genentech, San Francisco, CA, USA)
Smigelski, S.S (Development, Genentech, San Francisco, CA, USA)
Anchick, M.J (Medical Affairs, Genentech, San Francisco, CA, USA)

Contact Person: Robert B. Fick, Jr, MD (mittcptr@gene.com)


Abstract

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


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Fick, R.B.; Smigelski, S.S; Anchick, M.J; (1998). Anti-IgE as a Probe to Understand Allergic Inflammantion.. Presented at INABIS '98 - 5th Internet World Congress on Biomedical Sciences at McMaster University, Canada, Dec 7-16th. Invited Symposium. Available at URL http://www.mcmaster.ca/inabis98/denburg/fick0528/index.html
© 1998 Author(s) Hold Copyright