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

Laurian Zuidmeer-Jongejan ,Adriano Mari,Paula Garosi,Lars Blom,Marianne Witten,Carsten Bindslev‐Jensen,Ronald Van Ree,Rudolf Valenta,Enrico Scala,Ines Swoboda,Claudio Nicoletti,Birgit Linhart,Frank Stolz,Michael Clausen,Bettina M Jensen ,Joyce I Boye ,Rosaria Ferrara ,Lars K Poulsen ,Clare Mills ,Hanspeter Huber ,Sigurveig Sigurdardottir ,Antonio Portolés ,A Neubauer ,Stef J Koppelman ,Montserrat Fernández‐Rivas ,R Van Den Hout ,Juan A Asturias ,Heidi Julius Schnoor ,G Stavroulakis ,Alberto Martı́nez ,Anna Lewandowska–Polak ,Marek L Kowalski ,Bernard Maillère ,Serge A Versteeg ,Dirk Jan E Opstelten ,Neil M Rigby ,Nikolaos G Papadopoulos

doi:10.1186/2045-7022-2-5

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.

Highlights

Reliable figures are still largely unavailable, IgE-mediated food hypersensitivity is thought to affect around 1-2% of adults and 4-8% of children, i.e. roughly around 10 million EU inhabitants
Peach For peach (Prunus persica) allergy, we focus on its major allergen, the non-specific lipid transfer protein (LTP) Pru p 3
Concluding remarks The FAST project will increase our understanding on how to bring the treatment of food allergy to a higher level, i.e. by adding an alternative to the spectrum of treatment modalities for food allergy that is currently restricted to avoidance and rescue medication, and SLIT or OIT

Summary

Introduction

Reliable figures are still largely unavailable, IgE-mediated food hypersensitivity (hereafter referred to as food allergy) is thought to affect around 1-2% of adults and 4-8% of children, i.e. roughly around 10 million EU inhabitants (reviewed in [1,2]). The only available treatment for food allergy is avoidance, in conjunction with rescue medication in case of accidental exposure. Allergen-specific immunotherapy (SIT) is the only treatment available that targets the immunological cause of the disease. It has proven successful in treatment of insect venom allergies and for respiratory allergies such as rhino-conjunctivitis and asthma to pollen and house dust mite [5,6,7], but due to the duration and invasiveness (i.e. 3-5 years of monthly subcutaneous injections) and the risk of anaphylactic side-effects, SIT is a niche treatment compared to symptomatic drugs, though new alternative routes have been recently successfully explored [8]

Objectives

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Conclusion