Biomarker Developmental Unit

生物标志物开发单元

• 批准号: 10487347
• 负责人: Martin Stengelin
• 金额: $ 17.88万
• 依托单位: ARIZONA STATE UNIVERSITY-TEMPE CAMPUS
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-09-01 至 2027-08-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10487347
• 关键词: Address; Antibodies; Antibody Affinity; Antigens; Arizona; Autoantibodies; Autoantigens; B-Lymphocytes; Benign; Binding; Biological Assay; Biological Markers; Blinded; Blood Circulation; Breast; Clinical; Collaborations; Complement; Complex; Confidential Information; Detection; Development; Diagnostic; Diagnostic Procedure; Discrimination; Disease; Early Detection Research Network; Evaluation; Funding; Future; Glycoproteins; Goals; Government; Immune; Immunoassay; Institutes; Laboratories; Malignant Neoplasms; Malignant neoplasm of lung; Malignant neoplasm of ovary; Mass in breast; Monoclonal Antibodies; Nucleic Acids; Performance; Persons; Phase III Clinical Trials; Plasma; Procedures; Process; Production; Protein Array; Proteins; Reagent; Recombinant Proteins; Recombinants; Research; Resources; Sampling; Screening for cancer; Serology; Serology test; Signal Transduction; Speed; Spottings; TP53 gene; Testing; Translations; Universities; Vaccines; Validation; antigen detection; antimicrobial; assay development; base; biomarker development; biomarker discovery; cancer biomarkers; cancer type; circulating biomarkers; cohort; comparative; coronavirus disease; detection assay; extracellular vesicles; good laboratory practice; immunogenicity; industry partner; instrument; laboratory development; laboratory experiment; member; microbial; microorganism antigen; migration; multiplex assay; novel; novel marker; nucleic acid detection; operation; plasmid DNA; programs; protein biomarkers; radiological imaging; scale up; screening; serological marker; tumor; tumorigenesis; validation studies

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.

抽象的 亚利桑那州立大学 (ASU) 生物标记参考实验室 (BRL) 核心生物标记 表征中心 (BCC) 有两个主要目标，第一个目标是开发生物标志物的适应性测定。 Discovery Laboratory (BDL) 到 Meso Scale Diagnostics, LLC (MSD) 的商业检测平台。 BRL 的第二个目标是参与更大规模的 EDRN 协作验证研究。 支持分析的优化和验证以及诊断方法的改进。 亚利桑那州立大学和默沙东之间的合作旨在识别和验证与肺癌相关的生物标志物 和卵巢癌血清学标记物代表了一类有前途的早期癌症检测的新型标记物。 其中包括针对肿瘤异常蛋白的自身抗体 [AAb]、抗糖基化蛋白抗体 (AGPA) 针对癌症中异常糖基化的蛋白质，以及针对微生物的抗微生物抗体 由于癌症和良性疾病之间的微生物差异而产生不同的抗原。 产生抗体的 B 细胞，这些抗体在非常低的浓度和高浓度的情况下放大来自抗原的信号 肿瘤发生的早期阶段，此时相应的抗原本身可能无法在细胞中检测到。 循环。 亚利桑那州立大学生物设计研究所开发了一个高通量免疫蛋白质组学平台：核酸- 可编程蛋白质阵列 (NAPPA)，它取代了点样纯化蛋白质的复杂过程 发现质粒 DNA 并随后进行翻译的简单过程该平台用于识别有前途的产品。 默沙东的核心专长是开发和验证针对这两种癌症类型的候选抗体。 本提案针对的是多重免疫测定（直接分析物检测和血清学测定）。 转移已建立的肺癌和卵巢癌生物标志物以及 BCC 发现的生物标志物 BDL 到 MSD 平台上该平台适合大规模验证测试和未来的临床使用。 样品将在默沙东生物分析实验室和亚利桑那州立大学按照良好实验室规范 (GLP) 进行测试。 BDL 每年将有多达 10 种生物标记物被转移到 BRL 进行广泛的临床。 对最后一组大约十种癌症的标记物进行验证。 和/或抗原检测分析将被验证至实验室开发测试（LDT）所需的水平，并且 将开发支持生产约 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/或扩大规模 关键试剂，如重组蛋白或单克隆抗体、抗体亲和力成熟、蛋白质 检测开发、细胞外囊泡检测、核酸检测、多重面板开发、检测分析 在 MSD GLP 实验室进行验证和样品测试。