Project Summary/Abstract
The goal of the ASU Biomarker Characterization Center is to improve ovarian and lung cancer screening through
the development of biologically-relevant circulating immune biomarkers. The scientific approach of our Center is
based on several fundamental principles. First, that altered cancer protein expression, structure, and post-
translational modifications induce host autoantibodies to create circulating biomarkers. Second, that alterations
in microbial antigen expression (such as respiratory pathogens) also induce immunity, often detected in benign
rather than malignant disease. Third, that the protein modifications, as well as the immune response to these
neoantigenic structures, are heterogeneous between people, and that serologic biomarkers may complement
circulating protein biomarkers. We will take a systems immunology approach to discover three types of
antibodies, anti-microbial antibodies, autoantibodies and anti-aberrant glycoprotein antibodies. Our proposal
builds on our extensive experiences with cancer biomarker discovery and immunoproteomics technology
development. Our previous results on autoantibody biomarkers have been confirmed in blinded phase 2
multicenter validation studies and led to a CLIA-certified commercial blood test. Our results have shown that
multiplexed panels of autoantibodies are required for adequate predictive value. With prior EDRN support, we
have developed a set of innovative immunoproteomics technologies, namely high-density nucleic acid
programmable protein array (HD-NAPPA), contra-capture protein array (CCPA) and multiplexed in solution
protein array (MISPA), that, together with the largest full-length human and microbial gene collection at our
DNASU plasmid repository, enable us to study antibodies against the full human proteome, microbial proteomes
and the human O-glycoproteome for antibody biomarker signatures in cancer. Our Meso Scale Diagnostics
(MSD) team has fielded over 3,000 instruments worldwide, and over 700 commercially available biomarker assay
kits. Our expertise at serologic assay development was selected by Operation Warp Speed to use the V-PLEX®
serology panels as the basis of its standard binding assays for immunogenicity assessments in all funded Phase
III clinical trials of COVID vaccines. We will use our MSD MultiArray platform to migrate the top serologic and
protein markers for their utility in our target clinical applications. We will collaborate with experts on lung and
ovarian cancer screening at Vanderbilt University Medical Center, Boston University, MD Anderson Cancer
Center, and German Cancer Research Center, who will also provide access to high-quality well-characterized
samples to develop circulating biomarkers to enhance ovarian cancer screening or to distinguish benign from
malignant pulmonary nodules. Adhering to the principles of PRoBE design, we will perform Phase I discovery by
screening protein arrays with cancer patient and control sera for cancer or control-specific antibodies. Candidate
biomarkers for both lung and ovarian cancers will undergo Phase 2 validation.