FAST: towards safe and effective subcutaneous immunotherapy of persistent life-threatening food allergies

Clinical and Translational Allergy

Ronald van Ree⁶  Marianne Witten^1,14  Serge A Versteeg^1,11  Rob van den Hout³  Rudolf Valenta^1,12  Ines Swoboda^1,12  Frank Stolz⁴  George Stavroulakis⁸  Sigurveig T Sigurdardottir²  Heidi J Schnoor^1,14  Enrico Scala⁵  Neil Rigby^1,16  Antonio Portoles^1,17  Nikos G Papadopoulos⁸  Dirk-Jan Opstelten³  Claudio Nicoletti^1,16  Clare EN Mills¹  Alberto Martinez^1,15  Adriano Mari⁵  Bernard Maillere⁹  Birgit Linhart^1,12  Anna Lewandowska-Polak^1,18  Marek L Kowalski^1,18  Stef Koppelman³  Bettina M Jensen^1,14  Hans Huber⁴  Paula Garosi^1,16  Rosa Ferrara⁵  Michael Clausen²  Carsten Bindslev-Jensen⁷  Joyce Boye^1,13  Lars Blom^1,14  Juan Asturias^1,15  Angela Neubauer⁴  Lars K Poulsen^1,14  Montserrat Fernandez-Rivas^1,17  Laurian Zuidmeer-Jongejan^1,10 

[1] School of Translational Medicine, Manchester Academic Health Science Centre, Manchester Interdisciplinary Biocentre, University of Manchester, Manchester, UK;Landspitali University Hospital Reykjavik, Reykjavik, Iceland;HAL Allergy BV, Haarlem, The Netherlands;Biomay AG, Vienna, Austria;Center for Molecular Allergology, Istituto Dermopatico dell'Immacolata, Rome, Italy;Department of Otorhinolaryngology, Academic Medical Center, Amsterdam, The Netherlands;Odense University Hospital, Odense, Denmark;National Kapodistrian University of Athens, Athens, Greece;CEA, Institute of Biology Technologies, Paris, France;Department of Experimental Immunology, Academic Medical Center, Meibergdreef 9 1105, AZ, Amsterdam, The Netherlands;Department of Experimental Immunology, Academic Medical Center, Amsterdam, The Netherlands;Medical University of Vienna, Vienna, Austria;Food Research and Development Centre of Agriculture and Agri-Food Canada, St. Hyacinthe, Quebec, Canada;Allergy Clinic, Copenhagen University Hospital, Gentofte, Denmark;BIAL Aristegui, Bilbao, Spain;Institute of Food Research, Norwich, UK;Hospital Clinico San Carlos, Facultad de Medicina-UCM, IdISSC, Madrid, Spain;Medical University of Lodz, Lodz, Poland

关键词: Hypoallergens;    Peach;    Fish;    Sublingual;    Subcutaneous;    Specific immunotherapy;    Food allergy;    FAST;   

Others  :  794669
DOI  :  10.1186/2045-7022-2-5

 received in 2011-12-28, accepted in 2012-03-09,  发布年份 2012

【 摘 要 】

The FAST project (Food Allergy Specific Immunotherapy) aims at the development of safe and effective treatment of food allergies, targeting prevalent, persistent and severe allergy to fish and peach. Classical allergen-specific immunotherapy (SIT), using subcutaneous injections with aqueous food extracts may be effective but has proven to be accompanied by too many anaphylactic side-effects. FAST aims to develop a safe alternative by replacing food extracts with hypoallergenic recombinant major allergens as the active ingredients of SIT. Both severe fish and peach allergy are caused by a single major allergen, parvalbumin (Cyp c 1) and lipid transfer protein (Pru p 3), respectively. Two approaches are being evaluated for achieving hypoallergenicity, i.e. site-directed mutagenesis and chemical modification. The most promising hypoallergens will be produced under GMP conditions. After pre-clinical testing (toxicology testing and efficacy in mouse models), SCIT with alum-absorbed hypoallergens will be evaluated in phase I/II^a and II^b randomized double-blind placebo-controlled (DBPC) clinical trials, with the DBPC food challenge as primary read-out. To understand the underlying immune mechanisms in depth serological and cellular immune analyses will be performed, allowing identification of novel biomarkers for monitoring treatment efficacy. FAST aims at improving the quality of life of food allergic patients by providing a safe and effective treatment that will significantly lower their threshold for fish or peach intake, thereby decreasing their anxiety and dependence on rescue medication.

【 授权许可】

   
2012 Zuidmeer-Jongejan et al; licensee BioMed Central Ltd.

【 图 表 】

Figure 1.

Figure 2.

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