Department of Experimental Immunology, Academic Medical Center, Amsterdam, The Netherlands.
Clin Transl Allergy. 2012 Mar 9;2(1):5. doi: 10.1186/2045-7022-2-5.
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.
FAST 项目（食物过敏特异性免疫治疗）旨在开发安全有效的食物过敏治疗方法，针对常见、持续和严重的鱼类和桃过敏。经典的过敏原特异性免疫治疗（SIT），使用含有水的食物提取物的皮下注射可能有效，但已被证明伴随着太多的过敏反应副作用。FAST 的目标是通过用低变应原性重组主要过敏原替代食物提取物来开发一种安全的替代方法，作为 SIT 的有效成分。严重的鱼类和桃过敏分别由单一的主要过敏原，副肌球蛋白（Cyp c 1）和脂转移蛋白（Pru p 3）引起。正在评估两种方法来实现低变应原性，即定点突变和化学修饰。最有前途的低过敏原将在 GMP 条件下生产。在临床前测试（毒理学测试和小鼠模型中的功效）之后，将用 Alum 吸附的低过敏原进行 SCIT，在 I/IIa 和 IIb 期随机双盲安慰剂对照（DBPC）临床试验中进行评估，DBPC 食物挑战作为主要读出。为了深入了解潜在的免疫机制，将进行血清学和细胞免疫分析，允许鉴定用于监测治疗效果的新型生物标志物。FAST 的目标是通过提供安全有效的治疗方法来改善食物过敏患者的生活质量，这将显著降低他们对鱼类或桃的摄入阈值，从而减少他们的焦虑和对急救药物的依赖。
