血漿プロテオーム探索に関する会議 - 3日目

概要 | ショートコース | 1日目 | 2日目 | 3日目

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Wednesday, January 9

7:00am - 5:30 pm Registration Open

7:30 - 8:15 Breakfast Workshop Fabrication Challenges for Protein Microarrays

Sponsored by

Antonia Holway, Ph.D, Director of Microarray Applications,  Aushon BioSystems, Inc. The fabrication of antibody, protein and cell lysate microarrays presents unique challenges, both in terms of viscosity and buffer variations and the substrate types and coatings used. Aushon’s solid pin printing technology can reliably produce highly consistent arrays of these materials. Examples of protein array applications will be presented, including reverse phase lysate arrays applied to pathway analysis and the detection of cancer biomarkers.

8:15 Chairperson’s Remarks

8:20 Multianalyte Cancer Diagnostics on Microarrays of Antigens Measuring Cancer Specific Serum IgGs
Michael A. Tainsky, Ph.D. Barbara & Fred Erb Professor of Cancer Genetics, Department of Pathology; Director, Program in Molecular Biology and Genetics, Karmanos Cancer Institute, Wayne State University School of Medicine
There is enormous heterogeneity within any single type of cancer and therefore any diagnostic test that relies on a single marker for the early detection of cancer will be of limited accuracy. We have developed a high throughput method to bioselect large numbers of amino acid sequences of epitopes that react with antibodies specifically in the serum of cancer patients. The detection technology employs pattern recognition as a diagnostic rather than a single marker using specialized informatics techniques to interpret the results on numerous markers using protein chip technology. This platform is suitable to identify and validate a panel of antigen biomarkers for the early detection of cancer and because it is an antibody test it will be easily translated to clinical laboratories.

8:50 Filling the Gap between Discovery and Clinically Validated Biomarkers
Philip M. Hemken, Ph.D., Senior Scientist, Cancer Core R&D Life Sciences, Abbott Laboratories
The development of robust assays for biomarkers is an important step in filling the gap between the discovery and clinically validated biomarkers. First, the decision process to generate a biomarker assay for clinical use will be described. Second, the steps in the R&D process of developing a marker assay and evaluating clinical performance will be given in detail. The development of an ARCHITECT TIMP-1 (tissue inhibitor of metalloproteinases-1) immunoassay for colorectal cancer detection will be used as an example to demonstrate the types of pre-analytical and analytical performance testing that is necessary to validate a biomarker immunoassay. The overall emphasis will be to provide information for developing a robust immunoassay with as little analytical error as possible in order to confidently address the clinical utility of a biomarker.

9:20 Pancreatic Cancer Biomarker: From Discovery to Validation
Ru Chen, Ph.D., Research Assistant Professor, Medicine, University of Washington
Pancreatic cancer is a uniformly lethal disease which is difficult to diagnose at early stage and even more difficult to cure. Biomarkers for early detection are desperately needed. We use quantitative proteomics to analyze pancreatic tissue and pancreatic juice to identify candidate biomarkers. Candidate biomarkers are next validated by western blotting and immunohistochemistry in large cohort of patient samples, such as tissue arrays, and subsequently developed into diagnostic biomarkers in serum using ELISA and targeted proteomics.

9:50 Coffee Break in the Exhibit Hall

10:45 Biosensors, Biomarkers, Micropurification and Cancer
Edouard Nice, Professor, LRIC, FRSC, and Head, Protein Biosensing, Ludwig Institute for Cancer Research
We will demonstrate the potential of multidimensional chromatography and microaffinity-based reparative biosensor techniques to isolate complexes for the identification of signaling pathways involved in cancer, using downstream proteomics analysis. The development of sensitive affinity-based biosensor assays for biomarker evaluation and our approaches to the important topic of assay validation, using proteomic-based techniques developed in our laboratory to demonstrate assay specificity will also be illustrated.

11:15 Application of MS Based Biomarker Discovery from Lung Cancer Cell Lines and Tissues Toward the Development of a Lung Cancer Diagnostic Panel
Steven M. Ruben, Vice President, Proteomics, Celera
Because of the complexity and dynamic range of protein concentrations in human serum, we have implemented alternate approaches for discovery of novel biomarkers for lung cancer. Conditioned medium from tumor cell lines and cell surface discovery from tissues has led to a significant number of over-expressed protein candidates that are also at higher levels in the serum from lung cancer patients. In the future, panels of biomarkers from this discovery and validation effort may be useful in complementing helical CT screening or as a diagnostic screen on their own.

11:45 Development and Validation of a Diagnostic Assay
Nigel Clarke, Ph.D., Scientific Director, Quest Diagnostics
While the promise of proteomics is not doubted by many, the gulf between discovering a putative biomarker in a small size laboratory cohort converting that into a working diagnostic test has been sadly large. More and more commercial diagnostic laboratories are now turning their attention to this new frontier and are facing a multitude of issues. These new challenges are testing the current way commercial labs complete validations, even when dealing with validated, well-understood, existing biomarkers. This is especially true when using technologies new to such commercial labs such as LC-MS/MS. To this end development and validation of these biomarkers is forging a new mind-set in the industry that will continue to evolve over the coming years. An attempt to capture a flavor of this will be made in this presentation drawing on examples from our laboratory.

12:15pm Close of Morning Session

12:30 Luncheon Workshop 
or Lunch on Your Own 

1:45 Chairperson’s Remarks

Featured Presentation

1:50 From the Shelf to Clinical Practice - The BNP Success Story Alan Maisel, M.D., Professor, Medicine/Cardiology, San Diego VA Healthcare System This presentation will trace the evolution of the BNP test from, the initial idea, to pilot studies, to multinational trials, to FDA approval, to post-approval marketing studies. These successful experiences and insights provide eye-opening insider intelligence for researchers currently in the pipeline of biomarker discovery, development, validation, and commercialization process.

2:20 Protein C - A Multipurpose Biomarker for Severe Sepsis 
Mark D. Williams, M.D., Medical Director, Xigris Global Brand Development, Eli Lilly and Company
Sepsis is characterized by a systemic pro-inflammatory and pro-coagulant response to infection leading to the development of organ dysfunction (ie, severe sepsis). The Protein C pathway, originally thought to be solely an endogenous anticoagulant system, plays a major role in maintaining homeostasis during severe sepsis. Data from previous studies of Xigris (Recombinant Activated Protein C) show a strong association between protein C levels and mortality in patients with severe sepsis. Xigris uniquely increases Protein C levels in severe sepsis, which in part leads to the increase in survival. Currently, Xigris is dosed at 24 mcg/kg/hr for every patient with severe sepsis, no matter the severity or particular cause of the sepsis. We have recently implemented a novel biomarker-based clinical trial (RESPOND), which is designed to evaluate whether titrating the dose and duration of Xigris using serial Protein C levels can improve the benefit/risk. 

2:50 From PIF Identification to Clinical Applications Immunemodulatory Embryo-Derived Novel Peptide True BioMarker Dx and Nontoxic Rx Applications
Eytan R. Barnea, M.D., FACOG, Chief Scientist, BioIncept, LLC and Chairman, The Society for the Investigation of Early Pregnancy
Pregnancy is an immune paradox, in which the embryo avoids rejection without interfering with maternal systemic immunity, with no host-versus-graft or graft-versus-host response. PIF, the first message of viability and acceptance from the embryo/implant to mother/host, promotes maternal immune tolerance without suppression. PIF is nontoxic (embryo-derived), universally mammalian (cross-species effect), acts at low doses (nM), and its synthetic counterpart mimics the native peptidea™s features. A novel peptide (9-15 aa), this pro-receptive, pro-pregnancy peptide is measured by ELISA in maternal circulation reflects pregnancy viability from the 2-cell on and could lead to full pregnancy monitoring and specifically early in IVF to better embryo selection for transfer. These features furthermore match the desired profile for treating many immune disorders. Its immune modulatory effects were also successfully translated for testing in JDM, MS and GVHD models. A Phase I/II study for steroid resistant GVHD has been approved and is to be started shortly.

3:20 Identification of Surrogate Endpoints in Cancer Patients Using Parallel Profiling of Cancer Serum Biomarkers

Sponsored by

Robert Negm, Ph.D., Vice President, GenTel® BioSciences GenTel® BioSciences has developed a single capture antibody chip that can simultaneously screen dozens of circulating cancer serum biomarkers. The antibodies were validated for specificity and reproducibility. The abundance of over classical cancer biomarkers was measured directly from the serum of prostate cancer patients undergoing chemotherapy. Biomarker profiling data in the early stages of treatment of cancer patients may offer a novel clinical screening methodology to identify benefits of therapy during the early stages of treatment.

3:35 Refreshment Break in the Exhibit Hall

4:45 Poster Awards in the Exhibit Hall

 

Challenge Team Discussion

5:00 Challenges of Biomarker Development: Closing the Gap Between Discovery and Commercialization Moderator: Karin A. Hughes, Ph.D., Worldwide Product Director-Sepsis, Stroke & Protein C, Biosite Incorporated Topics for Discussion: Aspects of Biomarker Validation Clinical Utility Assay Robustness Platform Acceptance Regulatory Perspectiveworking with the FDA Partnering for Success

6:00 Close of Mining the Plasma Proteome Conference