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

基本信息

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
项目类别：
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

项目摘要

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且日益严重的健康问题，目前影响着美国 8% 的儿童我们。基于免疫学标记物 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价格昂贵，需要大量静脉切开术通常会导致假阳性和假阴性。在我们的第一阶段研究中， Enable Biosciences 创建了一种基于同型特异性的高度新颖的过敏免疫测试凝集PCR (ISAP) 技术。 ISAP 过敏检测面板可检测超过 80% 的常见过敏症状食物过敏原，包括花生、鸡蛋、牛奶、榛子、腰果和虾。与现有的不同方法，ISAP 只需要一微升的血液即可执行，从而更容易进行测试可能无法忍受大量抽血的儿童。 ISAP 显示 100% 特异性对所有食物过敏原的灵敏度为 75-100%，而现有方法的灵敏度为 38-60% 特异性和 71-96% 的灵敏度，使 ISAP 有可能大大减少误报和过敏测试呈阴性。 ISAP 还表现出非常低的测定间和测定内变异性（<15%）。最后，我们证明了 ISAP 可以适用于干血斑与血浆近乎完美的相关性 (R = 0.90-0.99)。建立在这些重要技术的基础上成就，使能已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 检测提供营销和自动化支持。我们正处于 CLIA 的最后阶段我们南旧金山实验室的认证，为我们创建了一个新的临床检测渠道 ISAP 测试的商业化。在此第二阶段提案中，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，我们将扩大现有的食物过敏小组，以涵盖 95% 的常见食物过敏原。其次，我们将使ISAP化学实现自动化，以降低劳动力成本并进一步提高再现性。第三，我们将生成并验证质量控制和制造协议以确保无缝的可扩展性。最后，我们将验证 ISAP 与干燥物质一起使用的适用性血斑样本可以进行侵入性更小的检测。该第二阶段提案可以通过增加可及性，彻底改变过敏测试并实现治疗成功，准确性和可重复性，同时降低患者和付款人的成本。