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TUESDAY, SEPTEMBER 14
7:00 am Registration Open
7:30-8:30 Morning Coffee
8:25-8:30 Chairperson’s Opening Remarks
8:30-9:00 Implementation of Individualized Protein Drug Target Activation Mapping for Personalized Medicine Trials in Oncology Today
Emanuel Petricoin, Ph.D., Co-Director, Center for Applied Proteomics and Molecular Medicine; Professor, Life Sciences, George Mason University
We have originated a functional protein pathway activation mapping technique, called the reverse phase protein microarray that we have now graduated to full clinical trial implementation. Using this technique, we can map and measure the activation of all FDA approved targeted inhibitors within each patient’s tumor for the first time ever. This information is now being used in ongoing first-of-their-kind clinical trials for breast and colorectal cancers that are true personalized therapy trials and the first ever for metastatic disease.
9:00-9:30 FDA Regulation of Protein-Based Diagnostic Tests
Jeffrey N. Gibbs, J.D., Director, Hyman, Phelps and McNamara, P.C.
The use of protein-based assays is expected to play an increasingly important role in medicine. Regulation by the Food and Drug Administration will strongly influence the extent to which this promise is fulfilled. New protein-based assays will need to go through the FDA review process before they can be commercially distributed. While laboratory developed tests are generally not being currently regulated by FDA, these assays may face greater regulatory scrutiny in the future. Understanding the FDA regulatory process will be critical for those individuals and companies seeking to commercialize protein-based assays.
9:30-10:00 Diagnostic and Treatment Monitoring Biomarkers for Intracellular Bacterial Infectious Disease
Eustache Paramithiotis, Ph.D., Senior Director, Cell & Molecular Biology, Caprion Proteomics, Inc.
Brucellosis is the world’s largest zoonosis. Diagnosis relies on serology or bacterial culture, both prone to false negatives. Treatment is by lengthy combination antibiotic therapy, with significant therapeutic failure, relapse, and adverse effects. Available biomarkers of relapse risk are not specific. Treatment monitoring biomarkers are not available. These limitations are common to most bacterial infections. To complement current diagnosis we propose to identify infection-specific proteins secreted by infected host cells, and follow these markers in sera. To identify treatment monitoring biomarkers we will identify serum protein expression changes associated with response to treatment, and develop assays for a multi-protein panel.
10:00-10:30 Streamlining the Regulatory Process of Multiplex Protein-Based Assays: An NCI and FDA Collaborative Effort
Emily Boja, Ph.D., Program Manager, Clinical Proteomic Technologies for Cancer, Center for Strategic Scientific Initiatives, National Cancer Institute, National Institutes of Health
The promise of protein biomarkers in cancer diagnostics is currently an area of considerable interest for application in personalized medicine. The rate of new protein analytes introduced, however, remains flat as reflected by an average of 0.3 cancer targets/year approved by the FDA. To close the gap between biomarker discovery and validation, the NCI-CPTC initiative has made significant progress since its inception to address analytical variability in current proteomic technologies/platforms, to introduce a bridging technology between these two distinct stages, and to collaborate with the FDA to understand regulatory science. This collaborative effort is highlighted in recently published workshop report and two mock 510(k) pre-submissions to illustrate the regulatory process of assay validation based on multiplex immunoaffinity MS and multiplex immunoaffinity array platforms.
10:30-11:30 Networking Coffee Break with Poster and Exhibit Viewing
11:30-12:00 pm Multiparameter Analysis of Circulating Tumor Cells in the Blood of Cancer Patients using a Process which Only Depletes Normal Cells
Jeffrey J. Chalmers, Ph.D., Professor, Department of Chemical and Biomolecular Engineering, The Ohio State University
We have developed a process which utilizes a unbiased negative enrichment protocol that depletes the normal blood cells to give an enriched and relatively pure CTC cell suspension. In this presentation we demonstrate that our technique is capable of detecting a significant number of CTCs in the peripheral blood of Head and Neck Cancer and Breast Cancer patients with high levels of sensitivity. Since the outcome of our negative depletion, enrichment process is a cell suspension; the final product can be further analyzed. By performing multiparameter microscopic analysis, we are able to find a significant number of circulating tumor cells which have down-regulated epithelial markers and upregulated mesenchymal markers and markers that have been suggested to be consisted with “cancer stem cells.”
12:00-12:30 In vivo High-Speed Photoacoustic Detection of Circulating Multiple Tumor Markers for Early Cancer Diagnosis and Personalized Therapy
Vladimir Zharov, Ph.D., Professor and Director, Philips Classic Laser & Nanomedicine Laboratories; Winthrop P. Rockefeller Cancer Institute, University of Arkansas for Medical Sciences
Recently we introduced a new platform of in vivo, noninvasive, photo-acoustic (PA) flow cytometry for detection of circuiting tumor cells (CTCs) targeted by conjugated nanoparticles directly in the bloodstream.1-2 This report summarizes new advances of this platform including multicolor high-pulse-repetition-rate laser arrays, ultra-fast signal acquisition algorithms, novel nanotechnology-based PA molecular contrast agents, and in vivo targeting of multiple markers in CTCs and tumor-associated nano- and microparticles. The study in vivo on tumor-bearing mouse models and spiked human blood samples demonstrates ultrahigh sensitivity of specificity for breast cancer CTCs and circulating particles that may be used for early cancer diagnosis and therapy selection when metastasis has not yet well developed and, hence well-timed therapy is more effective.
12:30-2:00 Lunch on Your Own
2:00-2:30 Circulating Mutant DNA as a Dynamic Cancer Biomarker
Luis Diaz, Ph.D., Assistant Professor, Oncology, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University
The recent advances in digital genomic have opened the doors to the clinical development of tumor-derived DNA as a biomarker for cancer screening, early detection, monitoring and measurement of early residual disease. The basis of this work is based on the well-accepted premise that cancer is defined by a discrete set of genetic alterations. This approach combines genomic sequencing with novel digital techniques to count tumor-derived DNA fragments in complex mixtures of DNA. The mutations found in cancers are never found in normal cell populations and detection of these mutations therefore confers exquisite specificity to the assay. Accordingly, he demonstrated that the level of mutations in the circulation [also known as circulating tumor DNA (ctDNA)] tracked with fluctuations in tumor burden in patients undergoing resective surgery for colorectal cancer. Most striking is the ability of ctDNA to accurately predict recurrence after surgery and monitor patients with undetectable CEA levels. This novel biomarker is based on personalized genomics that in essence provides a ‘viral load’ equivalent for patients with solid tumors.
2:30-3:00 Mutation Detection of Circulating Tumor Cells in Castration Resistant Prostate Cancer
Yuqiu Jiang, Ph.D., Principal Scientist, Molecular Technology Assessment, Veridex, LLC
Towards understanding molecular mechanisms of therapy response and drug resistance in patients, we sought to expand the utility of CellSearch technology to directly interrogate molecular markers in circulating tumor cells (CTCs). Here, we report a novel method, which combines CellSearch and WAVE® DHPLC technologies, for detecting gene mutations from peripheral-blood based on CTC enrichment. The androgen receptor gene mutation status was analyzed in 35 patients with castration resistant prostate cancer. 19 missense and 2 silent mutations, 5 deletions, and 1 insertion were observed in these CTC enriched samples. This approach has the potential to open new perspectives in understanding CTCs.
3:00-3:30 A Novel Approach for Finding and Characterizing CTCs
David Nelson, Ph.D., President and CEO, Epic Sciences, Inc.
Circulating tumor cells (“CTCs”) hold the promise to provide a readily accessible real-time fluid biopsy of tumors. CTCs would be immediately useful to Pharma and Biotech in clinical trials as secondary endpoints through counting CTCs. Molecularly characterizing CTCs would also be useful for guiding inclusion/exclusion decisions and, ultimately, as companion diagnostics for targeted therapies. In addition, CTCs are expected to be useful as a prognostic tool as well as for screening and staging. The key is finding enough CTCs in enough patients to be useful.
3:30-4:30 Networking Refreshment Break with Poster and Exhibit Viewing
4:30-5:00 Health Economics Outcomes Research for Innovative Diagnostic Technologies
Franz Hessel, M.D., M.P.H., Director, International Health Economics Outcomes Research, Abbott Diagnostics
The objective of HEOR studies is to demonstrate the relation of the patient-relevant clinical, epidemiological and patient-reported outcomes to the economic consequences of a defined health technology. Hereby often modeling techniques are used to estimate the cost-effectiveness. Although for pharmaceuticals in many countries HEOR studies are compulsory for reimbursement at a premium price so fare there is only a small number of HEOR studies for diagnostic tests available. Along the examples of uNGAL for the prediction of acute kidney injury in patients undergoing cardiac surgery, PLEX-ID as a new diagnostic approach in patients with severe sepsis, and HE4 as a new marker for ovarian cancer we show that innovative diagnostic tests have a high potential increase the medical benefit of the patients in a cost-effective or even cost-saving way.
5:00-5:30 Nanotechnologies for Molecular Diagnostics
Krassen Dimitrov, Ph.D., Group Leader, Australian Institute for Bioengineering and Nanotechnology, The University of Queensland, Australia
Direct digital counting (DDC) of biomolecules offers sizable advantages over traditional biodetection techniques in terms of accuracy, sensitivity, robustness and ease-of-use. Fluorescent nanobarcodes for single molecules rely on conventional microscopic technologies for their optical detection and identification. These fluorescent structures, or nanostrings, are already finding commercial applications and outperforming existing bioanalytical techniques. Electronic nanosensors with dimensions comparative to those of individual biomolecules are becoming feasible at the latest nodes of CMOS fabrication. Nanobarcodes for electronic detection with such electronic nanosensors would further advance miniaturization, cost-efficiency and throughput, however, they require fundamentally different technological approaches.
5:30 Close of Day