Multiplex food allergy diagnostic based on IgE immunologic markers

基于 IgE 免疫标记物的多重食物过敏诊断

• 批准号: 10011621
• 负责人: David Seftel
• 金额: $ 84.58万
• 依托单位: ENABLE BIOSCIENCES, INC.
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-08-08 至 2022-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10011621
• 关键词: Achievement; Affect; Agglutination; Agreement; Allergens; Allergic; Automation; Biological Assay; Biological Sciences; Blood; Blood Tests; Blood Volume; Blood specimen; Businesses; Cashew nut; Certification; Chemistry; Child; Childhood; Clinical; Clinical Trials; DNA; Development; Devices; Diagnosis; Diagnostic; Ensure; Evaluation; Exhibits; Food; Food Hypersensitivity; Generations; Hazelnuts; Health; Home environment; Hypersensitivity; IgE; Immunologic Markers; Immunologic Tests; Immunology; Immunotherapy; Infant; Juglans; Laboratories; Liquid substance; Manuals; Marketing; Measures; Methods; Milk; Monitoring Clinical Trials; Output; Patients; Performance; Phase; Plasma; Prevention; Prevention therapy; Process; Protocols documentation; Quality Control; ROC Curve; Reagent; Reproducibility; Risk; Robotics; Sampling; San Francisco; Secure; Sensitivity and Specificity; Shrimp; Signal Transduction; Specificity; Spottings; Technology; Test Result; Testing; Therapeutic; Transportation; United States; Validation; Variant; Venous; Venous blood sampling; Wheat; assay development; base; clinical trial enrollment; cohort; commercialization; cost; cross reactivity; design; egg; food allergen; food avoidance; improved; innovation; manufacturing process; next generation; novel; phase 1 study; product development; quality assurance; research clinical testing; software development; soy; success; testing services

Food allergy is a serious and growing health concern currently affecting 8% of children in the US. Blood tests based on the immunology marker IgE facilitate assessment of food allergy risks, and are required to recommend food avoidance or to implement new and innovative immunotherapies. However, current methods for allergy blood testing are expensive, require large volume phlebotomy and often result in false positives and negatives. In our Phase I study, Enable Biosciences created a highly novel allergy immune test based on Isotype-Specific Agglutination-PCR (ISAP) technology. This ISAP allergy panel detects over 80% of common food allergens, including peanut, egg, milk, hazelnut, cashew, and shrimp. Unlike existing methods, ISAP requires only a single microliter of blood to perform, facilitating easier testing in children who may not be able to endure large blood draws. ISAP displayed 100% specificity and 75-100% sensitivity for all food allergens in comparison to existing methods that exhibit 38-60% specificity and 71-96% sensitivity, giving ISAP the potential to greatly reduce false positives and negatives in allergy testing. ISAP also showed very low inter- and intra- assay variability (<15%). Finally, we demonstrated that ISAP can be adapted for use with dried blood spot with near perfect correlation with plasma (R = 0.90-0.99). Building upon these significant technical achievements, Enable has secured pivotal business partnerships with Hamilton Robotics to provide marketing and automation support for ISAP assays. We are in the final stage of CLIA certification for our South San Francisco laboratory, creating a new clinical testing channel for commercialization of ISAP tests. In this Phase II proposal, we seek support for further product development and quality control efforts to optimize ISAP testing for the clinical marketplace. First, we will expand our current food allergy panels to cover 95% of all common food allergens. Second, we will automate the ISAP chemistry to reduce labor costs and further improve reproducibility. Third, we will generate and validate quality control and manufacturing protocols to ensure seamless scalability. Finally, we will validate the suitability of ISAP for use with dried blood spot samples to permit even less invasive testing. This Phase II proposal can revolutionize allergy testing and enable therapeutic success by increasing accessibility, accuracy and reproducibility while reducing costs for patients and payors alike.

食物过敏是一个严重的和日益增长的健康问题，目前影响到8%的儿童， 我们基于免疫学标志物IgE的血液测试有助于评估食物过敏风险， 并被要求建议避免食物或实施新的和创新的 免疫疗法然而，目前的过敏血液检测方法是昂贵的，需要 大体积静脉切开术，并经常导致假阳性和假阴性。在我们的第一阶段研究中， 埃能宝生物科学公司开发了一种基于同种型特异性的高度新颖的过敏免疫测试。 凝集-PCR（ISAP）技术。这种ISAP过敏面板检测超过80%的常见 食物过敏原，包括花生、鸡蛋、牛奶、榛子、腰果和虾。不同于现有 方法，ISAP只需要一微升的血液来执行，便于更容易的测试， 可能无法忍受大量抽血的儿童。ISAP显示100%特异性， 75-100%的灵敏度为所有食物过敏原相比，现有的方法，表现出38-60% 特异性和71-96%的灵敏度，使ISAP有可能大大减少假阳性， 过敏测试呈阴性ISAP还显示出非常低的试验间和试验内变异性 （<15%）。最后，我们证明了ISAP可以适用于干血斑， 与血浆的相关性接近完美（R = 0.90-0.99）。基于这些重要的技术 为了取得这些成就，Enable与汉密尔顿机器人公司建立了关键的业务合作伙伴关系， 为ISAP分析提供市场营销和自动化支持。我们正处于CLIA的最后阶段 为我们的南旧金山弗朗西斯科实验室获得认证，为 ISAP测试的商业化。在第二阶段的提案中，我们寻求对进一步产品的支持， 开发和质量控制工作，以优化临床市场的ISAP测试。 首先，我们将扩大我们目前的食物过敏小组，以涵盖95%的常见食物过敏原。 其次，我们将自动化ISAP化学，以降低劳动力成本，并进一步提高 再现性第三，我们将制定和验证质量控制和制造协议 以确保无缝扩展性。最后，我们将验证ISAP是否适合用于干燥的 血斑样本，以允许更少的侵入性测试。第二阶段的建议可以 革新过敏测试，通过增加可及性实现治疗成功， 准确性和可重复性，同时为患者和付款人降低成本。