FAST

TOWARDS SAFE AND EFFECTIVE IMMUNOTHERAPY OF PERSISTENT LIFE-THREATENING FOOD ALLERGIES

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 Obiettivo del progetto (Objective)

'The FAST project aims at the development of safe and effective treatment of food allergies. It targets persistent and severe allergy to fish and fruit. Besides persistence and severity, this choice is based on prevalence and the importance of these foods for a healthy diet. Classical allergen-specific immunotherapy (SIT) for treatment of food allergy using subcutaneous injections with food extracts has proven to be effective but too dangerous due to anaphylactic side-effects. FAST will therefore develop a safe alternative by replacing food extracts with hypo-allergenic recombinant major allergens, the active ingredients of SIT. Both severe fish and fruit allergy are caused by a single major allergen, parvalbumin for fish and lipid transfer protein for fruit. This makes development of a novel biotechnological product feasible. Two approaches will be evaluated for achieving hypoallergenicity, i.e. site-directed mutagenesis and chemical modification. The most promising hypo-allergenic versions of parvalbumin and lipid transfer protein will be produced under GMP conditions. After pre-clinical testing (toxicology testing and efficacy in mouse models), Phase I and II randomized double-blind placebo-controlled multi-center clinical trials will be performed. Two routes of administration will be evaluated, subcutaneous in case of fish and sublingual in case of fruit. The primary read-out will be the double-blind placebo-controlled food challenge. To understand the underlying immune mechanisms of subcutaneous and sublingual immunotherapy, these trials will be accompanied by in depth serological and cellular immune analyses, allowing identification of novel biomarkers for monitoring treatment efficacy. FAST will improve the quality of life of food allergic patients by providing a safe and effective curative treatment that will end their dependence on avoidance and rescue medication.'

Introduzione (Teaser)

Most food allergies are chronic lifelong diseases affecting around 10 million Europeans. A curative treatment for food allergies is the only way to alleviate these potentially life-threatening conditions.

Descrizione progetto (Article)

Current treatment for food allergies is total avoidance and rescue treatment such as epinephrine injection in the event of inadvertent exposure. Some allergies have been treated by allergen-specific immunotherapy (SIT), where patients receive monthly injections with allergen extracts for 3 to 5 years. However, SIT cannot be used to treat food allergies because of the severity and unpredictability of reaction.

The project 'Towards safe and effective immunotherapy of persistent life-threatening food allergies' (http://www.allergome.org:8080/fast/index.jsp (FAST)) aims to find effective treatment solutions for food allergies. The objective is to modify the allergens to make them less potent before using them for testing in clinical trials in multiple centres.

Fish allergy has been linked to parvalbumin and severe reactions to fruit have been linked to lipid transfer protein. The chemical modification of allergens using glutaraldehyde has been successful. Site-specific genetic modification of allergens were also attempted to make them hypoallergenic. Moreover, oral and subcutaneous injections of the recombinant hypoallergenic allergens were investigated for efficacy and side effects.

FAST project members have developed four fish and seven fruit allergen preparations. These preparations were tested for hypoallergenicity, immunogenicity and stability under different storage conditions. A protocol has been developed for a placebo-controlled multi-centre double-blind study. Data is being collected from 30 patients allergic to fish and fruit to identify markers and monitor the efficacy of allergy treatment.

Tests led to successful development of the hypoallergenic molecule for fish immunotherapy. The expression of this molecule was optimised for good manufacturing practices production and is in the last stages of quality control before it can be used in toxicity and stability testing.

None of the candidate molecules for the fruit allergen fulfilled the criteria for selection. Therefore, partners decided to come up with a strategy to design alternative hypoallergenic and immunogenic molecules with acceptable stability. Less disruptive strategies were chosen to avoid major changes in the structure of the molecules.

Child and adult nutrition is affected by allergies to fish and fruit, which are a key part of a healthy diet. FAST could be successful in finding a safe solution to food allergies that will solve a major problem with nutrition due to diet limitations.