Biomarker Developmental Unit

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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.