Open Access Highly Accessed Review

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

Laurian Zuidmeer-Jongejan118*, Montserrat Fernandez-Rivas2, Lars K Poulsen3, Angela Neubauer4, Juan Asturias5, Lars Blom3, Joyce Boye6, Carsten Bindslev-Jensen7, Michael Clausen8, Rosa Ferrara9, Paula Garosi10, Hans Huber4, Bettina M Jensen3, Stef Koppelman11, Marek L Kowalski12, Anna Lewandowska-Polak12, Birgit Linhart13, Bernard Maillere14, Adriano Mari9, Alberto Martinez5, Clare EN Mills1015, Claudio Nicoletti10, Dirk-Jan Opstelten11, Nikos G Papadopoulos16, Antonio Portoles2, Neil Rigby10, Enrico Scala9, Heidi J Schnoor3, Sigurveig T Sigurdardottir8, George Stavroulakis16, Frank Stolz4, Ines Swoboda13, Rudolf Valenta13, Rob van den Hout11, Serge A Versteeg1, Marianne Witten3 and Ronald van Ree117

Author Affiliations

1 Department of Experimental Immunology, Academic Medical Center, Amsterdam, The Netherlands

2 Hospital Clinico San Carlos, Facultad de Medicina-UCM, IdISSC, Madrid, Spain

3 Allergy Clinic, Copenhagen University Hospital, Gentofte, Denmark

4 Biomay AG, Vienna, Austria

5 BIAL Aristegui, Bilbao, Spain

6 Food Research and Development Centre of Agriculture and Agri-Food Canada, St. Hyacinthe, Quebec, Canada

7 Odense University Hospital, Odense, Denmark

8 Landspitali University Hospital Reykjavik, Reykjavik, Iceland

9 Center for Molecular Allergology, Istituto Dermopatico dell'Immacolata, Rome, Italy

10 Institute of Food Research, Norwich, UK

11 HAL Allergy BV, Haarlem, The Netherlands

12 Medical University of Lodz, Lodz, Poland

13 Medical University of Vienna, Vienna, Austria

14 CEA, Institute of Biology Technologies, Paris, France

15 School of Translational Medicine, Manchester Academic Health Science Centre, Manchester Interdisciplinary Biocentre, University of Manchester, Manchester, UK

16 National Kapodistrian University of Athens, Athens, Greece

17 Department of Otorhinolaryngology, Academic Medical Center, Amsterdam, The Netherlands

18 Department of Experimental Immunology, Academic Medical Center, Meibergdreef 9 1105, AZ, Amsterdam, The Netherlands

For all author emails, please log on.

Clinical and Translational Allergy 2012, 2:5  doi:10.1186/2045-7022-2-5

Published: 9 March 2012

Abstract

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/IIa and IIb 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.

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