Biomarker Developmental Unit

摘要 亚利桑那州立大学(ASU)生物标记参考实验室(BRL)核心 表征中心(BCC)有两个主要目标。第一个是调整在Biomarker中开发的分析方法 从中尺度诊断有限责任公司的发现实验室(BDL)到商业分析平台。(MSD)用于 临床验证。BRL的第二个目标是参与更大规模的EDRN协作验证研究， 支持分析方法的优化和验证以及诊断方法的改进。 亚利桑那州立大学和MSD的这项合作旨在识别和验证与肺癌相关的生物标记物 和卵巢癌。血清学标志物代表了一类很有前途的癌症早期检测的新标志物。 这些包括针对肿瘤异常蛋白的自身抗体[AABS]、抗糖化蛋白抗体 (AGPA)抗癌中异常糖基化的蛋白质，以及抗微生物抗体 由于癌症和良性疾病之间的微生物差异而产生的不同抗原。通过复制 产生抗体的B细胞，这些抗体在很低的浓度下放大来自抗原的信号，并在 在肿瘤形成的早期阶段，相应的抗原本身可能在 发行量。 亚利桑那州立大学生物设计院开发了高通量免疫蛋白质组学平台：核酸- 可编程蛋白质阵列(NAPPA)，它取代了复杂的分离纯化蛋白质的过程 简单的过程是点出质粒DNA，然后翻译。这个平台被用来识别有希望的 两种癌症的候选抗体。MSD的核心专长是开发和验证Robust 多重免疫分析(直接分析物检测和血清学分析)。本提案是针对 转移BCC发现的已建立的肺癌和卵巢癌生物标志物和生物标志物 Bdl安装到MSD平台上。该平台适合大规模的验证测试和未来的临床应用。 样品将在MSD的生物分析实验室根据良好的实验室规范(GLP)和亚利桑那州立大学进行测试。 每年最多有10个生物标记物将被转移到BRL。BDL将进行广泛的临床试验 对两种癌症的标志物进行下调选择的验证。对最后一套大约10种血清学的检测 和/或抗原检测分析将被验证到实验室开发测试(LDT)所需的水平，以及 将制定支持生产约10,000个样品的试剂盒的制造程序。 BCC BRL与EDRN成员的其他合作可能包括开发和/或扩展 关键试剂，如重组蛋白或单抗、抗体亲和力成熟、蛋白质 检测发展，细胞外小泡检测，核酸检测，多重面板开发，检测 在MSD的GLP实验室进行验证和样本测试。

Abstract The Biomarker Reference Laboratory (BRL) core of the Arizona State University (ASU) Biomarker Characterization Center (BCC) has two primary goals. The first is to adapt assays developed in the Biomarker Discovery Laboratory (BDL) to the commercial assay platform from Meso Scale Diagnostics, LLC. (MSD) for clinical validation. The second goal of the BRL is to participate in larger EDRN collaborative validation studies, with support for optimization and verification of assays and improvement of diagnostic methods. This collaboration between ASU and MSD aims to identify and validate biomarkers related to lung cancer and ovarian cancer. Serological markers represent a promising class of novel markers for early cancer detection. These include autoantibodies [AAbs] against aberrant proteins from tumors, anti-glycosylated protein antibodies (AGPA) against proteins aberrantly glycosylated in cancer, and anti-microbial antibodies against microbial antigens that differ due to microbial differences between cancer and benign disease. Through replication of antibody-producing B-cells, these antibodies amplify a signal from antigens at very low concentrations and at an early stage in tumorigenesis when the corresponding antigens may not themselves be detectable in the circulation. ASU’s Biodesign Institute developed a high-throughput immunoproteomics platform: Nucleic Acid- Programmable Protein Array (NAPPA), which replaces the complex process of spotting purified proteins with the simple process of spotting plasmid DNA followed by translation. This platform was used to identify promising antibody candidates for both cancer types. MSD’s core expertise is development and validation of robust multiplexed immunoassays (direct analyte detection and serology assays). The present proposal is directed towards transferring established lung and ovarian cancer biomarkers and biomarkers discovered by the BCC BDL onto the MSD platform. This platform is appropriate for large-scale validation testing and future clinical use. Samples will be tested in MSD’s Bioanalytical Laboratory under Good Laboratory Practice (GLP) and at ASU. Up to ten biomarkers per year will be transferred to the BRL. The BDL will perform extensive clinical validation to downselect markers for both types of cancer. Assays for the final set of approximately ten serology and/or antigen detection assays will be validated to a level required for a Laboratory Developed Test (LDT) and manufacturing procedures that would support the production of kits for ~10,000 samples will be developed. Additional collaborations of the BCC BRL with EDRN members may include development and/or scale-up of critical reagents such as recombinant proteins or monoclonal antibodies, antibody affinity maturation, protein assay development, extracellular vesicle detection, nucleic acid detection, multiplex panel development, assay validation, and sample testing in MSD’s GLP laboratory.