U2CCA271903

High-Throughput Immunoproteomics for Cancer Biomarker Discovery - 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, we believe that altered cancer protein expression, structure, and post-translational modifications induce host autoantibodies to create circulating biomarkers. Second, we recognize that alterations in microbial antigen expression, such as respiratory pathogens, also induce immunity, often detected in benign rather than malignant disease. Third, we understand 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. We 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). Together with the largest full-length human and microbial gene collection at our DNASU Plasmid Repository, these technologies 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 offers over 700 commercially available biomarker assay kits. Our expertise in 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. These collaborators 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 II validation.

Arizona State University

TO IMPROVE SCREENING AND EARLY DETECTION STRATEGIES AND TO DEVELOP ACCURATE DIAGNOSTIC TECHNIQUES AND METHODS FOR PREDICTING THE COURSE OF DISEASE IN CANCER PATIENTS. SCREENING AND EARLY DETECTION RESEARCH INCLUDES DEVELOPMENT OF STRATEGIES TO DECREASE CANCER MORTALITY BY FINDING TUMORS EARLY WHEN THEY ARE MORE AMENABLE TO TREATMENT. DIAGNOSIS RESEARCH FOCUSES ON METHODS TO DETERMINE THE PRESENCE OF A SPECIFIC TYPE OF CANCER, TO PREDICT ITS COURSE AND RESPONSE TO THERAPY, BOTH A PARTICULAR THERAPY OR A CLASS OF AGENTS, AND TO MONITOR THE EFFECT OF THE THERAPY AND THE APPEARANCE OF DISEASE RECURRENCE. THESE METHODS INCLUDE DIAGNOSTIC IMAGING AND DIRECT ANALYSES OF SPECIMENS FROM TUMOR OR OTHER TISSUES. SUPPORT IS ALSO PROVIDED FOR ESTABLISHING AND MAINTAINING RESOURCES OF HUMAN TISSUE TO FACILITATE RESEARCH. SMALL BUSINESS INNOVATION RESEARCH (SBIR) PROGRAM: TO EXPAND AND IMPROVE THE SBIR PROGRAM, TO INCREASE PRIVATE SECTOR COMMERCIALIZATION OF INNOVATIONS DERIVED FROM FEDERAL RESEARCH AND DEVELOPMENT, TO INCREASE SMALL BUSINESS PARTICIPATION IN FEDERAL RESEARCH AND DEVELOPMENT, AND TO FOSTER AND ENCOURAGE PARTICIPATION OF SOCIALLY AND ECONOMICALLY DISADVANTAGED SMALL BUSINESS CONCERNS AND WOMEN-OWNED SMALL BUSINESS CONCERNS IN TECHNOLOGICAL INNOVATION. SMALL BUSINESS TECHNOLOGY TRANSFER (STTR) PROGRAM: TO STIMULATE AND FOSTER SCIENTIFIC AND TECHNOLOGICAL INNOVATION THROUGH COOPERATIVE RESEARCH AND DEVELOPMENT CARRIED OUT BETWEEN SMALL BUSINESS CONCERNS AND RESEARCH INSTITUTIONS, TO FOSTER TECHNOLOGY TRANSFER BETWEEN SMALL BUSINESS CONCERNS AND RESEARCH INSTITUTIONS, TO INCREASE PRIVATE SECTOR COMMERCIALIZATION OF INNOVATIONS DERIVED FROM FEDERAL RESEARCH AND DEVELOPMENT, AND TO FOSTER AND ENCOURAGE PARTICIPATION OF SOCIALLY AND ECONOMICALLY DISADVANTAGED SMALL BUSINESS CONCERNS AND WOMEN-OWNED SMALL BUSINESS CONCERNS IN TECHNOLOGICAL INNOVATION.

93.394 - Cancer Detection and Diagnosis Research

National Cancer Institute (NCI) [HHS - NIH]

Arizona United States

State-Wide

The Early Detection Research Network: Biomarker Characterization Centers (U2C Clinical Trial Not Allowed) (RFA-CA-21-035)

Amendment Since initial award the total obligations have increased 256% from $710,300 to $2,531,373.