Synthetic calibrators for immunohistochemical assays

本提案的目的是开发和验证临床免疫组织化学(IHC)分析的合成校准标准。IHC检测是癌症诊断和外科病理学的标准检测方法，但其固有的可变性存在严重问题。缺乏标准化的测试材料阻碍了测试的准确性，这阻碍了建立统一和定量的方法和诊断标准。大多数临床IHC检测检测到的细胞抗原是生产用作对照的昂贵的。细胞学通过发展噬菌体展示方法来产生细胞抗原的多肽模拟物，作为天然抗原的替代品，从而解决了这个问题。现在，我们建议生产用于显微镜定量成像系统的精确、定量的IHC校准标准。一套载玻片上的校准器将控制分析的可变性，这可能是由于试剂降解或分析错误造成的。第二套处理校准器将控制分析前的可变性，这与组织固定或抗原修复有关。这项工作将导致IHC校准标准的临床验证试验的第二阶段提案。为重要的药物诊断分析制定统一的IHC校准标准将把组织病理学实验室的质量控制提升到其他产生定量数据的临床实验室的水平。拟议的商业应用：本提案中描述的技术将为临床免疫组织化学分析的质量控制提供第一个商业化生产的定量标准。标准对于确定化验可变性的来源和确保患者检测结果的准确性和重复性是重要的，无论哪个实验室进行检测。

The objective of this proposal is to develop and validate synthetic calibration standards for clinical immunohistochemical (IHC) assays. IHC assays are the standard of care in cancer diagnosis and surgical pathology, but they suffer from a serious problem with inherent variability. Accuracy in testing is hampered by the lack of standardized test materials, which prevents the establishment of uniform and quantitative methods and diagnostic criteria. Most clinical IHC assays detect cellular antigens that are expensive to produce for use as controls. CytoLogic solved this problem by developing phage display methods to produce peptide mimics of cellular antigens, which serve as surrogates for native antigens. Now, we propose to produce, precise, quantitative IHC calibration standards for use with microscope-based quantitative imaging systems. One set of on-slide calibrators will control for analytic variability, which can result from reagent degradation or assay errors. A second set of processing calibrators will control for pre-analytic variability, which is associated with tissue fixation or antigen retrieval. This work will lead to a Phase II proposal for clinical validation trials for the IHC calibration standards. Development of uniform IHC calibration standards for important pharmacodiagnostic analytes will elevate quality control in the histopathology laboratory to the level of other clinical laboratories that produce quantitative data. PROPOSED COMMERCIAL APPLICATIONS: The technology described in this proposal will provide the first commercially produced quantitative standard for quality control of clinical immunohistochemical assays. Standards are important to identify sources of assay variability and to ensure that patient test results are accurate and reproducible regardless of which laboratory performs them.