Circulating Tumor Cells and Liquid Biopsy

The field of liquid biopsy is moving beyond isolation and characterization of CTCs and ctDNA to surveillance, early detection of relapse and minimal residual disease, and interventional studies in clinical applications. The scope of the conference encompasses circulating tumor cells, cell-free circulating DNA, exosomes and extracellular vesicles. This meeting has become an important annual event for leaders in the community to discuss the tools, validation and implementation of circulating biomarkers, which are transforming our understanding and management of disease. Join us this February for the most comprehensive and largest event on this topic.

Scientific Advisory Board

Stefanie Jeffrey, M.D., John and Marva Warnock Professor, Surgery; Chief, Surgical Oncology Research, Stanford University School of Medicine

Klaus Pantel, M.D., Professor and Founding Director, Institute of Tumor Biology, University, Medical Center Hamburg-Eppendorf

Steven A. Soper, Ph.D., Professor, Micro and Nanofabricated Tools for Biological Discovery and Medical Diagnostics, University of Kansas

Shannon L. Stott, Ph.D., Assistant Professor, Department of Medicine, Massachusetts General Hospital, Harvard Medical School; BioMEMS Resource Center, The MGH Cancer Center

 

Monday, February 12

10:30 am Conference Program Registration Open

OPENING KEYNOTE SESSION: CLINICAL INTEGRATION OF LIQUID BIOPSY

11:50 Chairperson’s Opening Remarks

Stefanie Jeffrey, M.D., John and Marva Warnock Professor, Surgery; Chief, Surgical Oncology Research, Stanford University School of Medicine

12:00 pm Phenogenomic Subtyping of CTCs to Identify Biomarkers that Improve Prostate Cancer Patient Outcomes

Howard I. Scher, M.D., Chief & Medical Oncologist, Genitourinary Oncology Services, Memorial Sloan Kettering Cancer Center

12:30 The Emerging Landscape for Liquid Biopsy Technologies: A Perspective from the NCI

Anthony Dickherber, Ph.D., Program Director, Center for Strategic Scientific Initiatives, National Cancer Institute

The U.S. National Cancer Institute (NCI) is the world’s largest cancer research-focused funding organization, and thereby serves a critical role in identifying and investing in timely research opportunities, including those advancing us towards the various promises of liquid biopsies for better clinical management of cancer. An overview of NCI related technology investment strategies and the emerging trends observed through those investments will be described.

1:00 Session Break

1:10 Luncheon Presentation I: Multiplexed Sample to Answer Applications for Liquid Biopsy Solutions

Paul Smith, CEO, ANGLE Biosciences

Circulating tumor cells (CTCs) represent a potentially rich source of information for cancer diagnostics (e.g. diagnosis, staging, prognosis, or monitoring) and therapeutic decision-making throughout the course of patient management. Molecular characterization of CTCs may help in the identification of tumor histotype, transition to invasive phenotypes, and/or mutation status. This talk will highlight the coupling of two technologies to enable multiplex gene expression profiling of CTCs.


1:40 Luncheon Presentation II: A Newly Discovered Stromal Cell Found in Blood Enables the Detection and Diagnosis of Cancer When it Matters Most

Daniel Adams, Senior Research Scientist, Creatv MicroTech, Inc.

Cha-Mei Tang, Sc.D., President and CEO, Creatv MicroTech, Inc.

A stromal cell we discovered in the blood of cancer patients, called Cancer Associated Macrophage-like cell (CAML), is found in a wide variety of solid tumor samples analyzed, and in all stages of cancer. They are found more often than CTCs. CAML and CTCs are collected at the same time on CellSieveTM microfilter. They are applicable to cancer screening, early detection of cancer recurrence, prognosis, companion diagnostics and monitoring of therapeutic response.

2:10 Session Break

BRINGING CLINICAL UTILITY TO LIQUID BIOPSY - LATEST CLINICAL RESULTS

2:30 Chairperson’s Remarks

Klaus Pantel, M.D., Professor and Founding Director, Institute of Tumor Biology, University Medical Center Hamburg-Eppendorf

2:40 Interrogating the AR in Advanced Prostate Cancer Using Liquid Biopsies: Resistance Mechanisms and Therapeutic Targeting

Emmanuel Antonarakis, M.D., Associate Professor, Urologic Oncology, Johns Hopkins University

The androgen receptor (AR) remains the most crucial therapeutic target for prostate cancer therapy. However, several molecular mechanisms of response and resistance to AR-targeting prostate cancer therapies have recently been elucidated. This talk will review blood-based analysis of the AR for copy-number alterations, mutations, and splicing abnormalities in an effort to understand AR-therapy resistance and novel therapeutic approaches.

3:10 Liquid Biopsy in Breast Cancer: From Discovery to Clinical Utility

Klaus Pantel, M.D., Ph.D., Professor, Department Chair, Institute of Tumor Biology, University Medical Center Hamburg-Eppendorf

Liquid biopsy provides prognostic information and serves to identify therapeutic targets or mechanisms of resistance to therapy in cancer patients. Metastatic cells might have unique characteristics that can differ from the bulk of cancer cells in the primary tumor currently used for stratification of patients to systemic therapy. Moreover, real-time monitoring of circulating tumor cells (CTCs) and cell-free DNA provide unique information for the clinical management of cancer patients.

3:40 Chemistry-Free Microfluidic Technologies to Sort Circulating Tumor Cells and Clusters from Patient Whole Blood

Gozde Durmus, Ph.D., Postdoctoral Fellow, Biochemistry, Stanford University School of Medicine

Micro- and nano-scale technologies can have a significant impact on medicine and biology in the areas of cell manipulation, diagnostics and monitoring. Our research is centered on finding solutions for real world problems at the clinic. We will present an overview of our lab's work in magnetic levitation for assembling cells and chemistry-free sorting of rare cells from whole blood. Our levitation platform uniquely enables ultrasensitive density measurements, imaging, and profiling of cells in real-time at single-cell resolution. This method has broad applications in the label-free identification and sorting of CTCs and CTM, and in drug screening for personalized medicine. We will also share our efforts in developing new tools to isolate extracellular vesicles from blood, urine and cell cultures, and the broader clinical implications these technologies could have in medicine.

4:10 Parallelization of NGS Library Preparation

Derek Bogdanoff, Research Associate, Center for Advanced Technologies, University of California at San Francisco

An overview of different sequencing library prep and barcoding methods prepared at the nanolitre scale will be presented. In particular, a new single-cell dispensing/microwell platform will be described. It offers a number of advantages in the use and preparation of parallel NGS libraries.

4:40 Refreshment Break and Transition to Plenary Session

5:00 Plenary Keynote Session (click here for more details)

 

Precision for Medicine

6:00 Grand Opening Reception in the Exhibit Hall with Poster Viewing

7:30 Close of Day

Tuesday, February 13

7:30 am Registration Open and Morning Coffee

8:00 Plenary Keynote Session (click here for more details)

9:00 Refreshment Break in the Exhibit Hall with Poster Viewing

LIQUID BIOPSY DEVELOPMENT

10:05 Chairperson’s Remarks

Stefanie Jeffrey, M.D., John and Marva Warnock Professor, Surgery; Chief, Surgical Oncology Research, Stanford University School of Medicine

10:15 FEATURED PRESENTATION: Circulating Tumor Cells: History and Future Perspectives

Jonathan W. Uhr, M.D., Professor Emeritus, Immunology, University of Texas Southwestern Medical Center

The modern era of CTC analysis began 2 decades ago and gained momentum when CellSearch was approved by the FDA. The changes of CTC counts allowed prognostication of patients with growing cancers. Genotypic and immunophenotypic analyses will play critical roles in personalized treatment for cancer.

10:45 Microfluidic Cell Tethering to Identify Anti-Metastasis Drugs

Stuart S. Martin, Ph.D., Professor, Physiology, Marlene and Stewart Greenebaum NCI Comprehensive Cancer Center, University of Maryland School of Medicine

11:15 Dissecting Mechanisms of Breast Cancer Metastasis Using Patient-Derived Circulating Tumor Cells

Min Yu, M.D., Ph.D., Assistant Professor, Stem Cell Biology and Regenerative Medicine Member, Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California

Circulating tumor cells (CTCs) are expected to contain metastasis-initiating cells that can shed light on the mechanisms of cancer metastasis. However, due to limited patient-derived material, the metastatic capability of CTCs has yet to be proved. Using our recently established patient-derived CTC lines, we found that different patient CTC lines demonstrated distinct metastatic tissue tropisms in immunodeficient mice and identified associated pathways to specific organs via RNA-seq and ATAC-seq analysis.

11:45 Isolating and Characterizing Clinically Relevant CTCs Using the VTX-1 Liquid Biopsy System 

Elodie Sollier, Ph.D., CSO, Research and Development, Vortex Biosciences, Inc.

12:15 Session Break

12:25 Luncheon Presentation I: Achieving Clinical Utility of Cell-Based Liquid Biopsy

Mark Connelly, PhD, Chief Industrial Operation, R&D Officer, US Menarini Silicon Biosystems Inc

Clinical studies have demonstrated that CTCs enumeration is a strong, independent predictor of overall and progression-free survival in metastatic breast, prostate and colorectal cancer at any time during the course of disease. The field agrees that for a full adoption of liquid biopsy as clinical diagnostic tool to guide therapeutic decision the molecular characterization of CTCs is necessary.

1:25 Refreshment Break in the Exhibit Hall with Poster Viewing

NEW TOOLS FOR LIQUID BIOPSY – WAY OF THE FUTURE

2:00 Chairperson’s Remarks

Steven A. Soper, Ph.D., Foundation Distinguished Professor, Chemistry, Mechanical Engineering, University of Kansas

2:10 CTC Isolation Platforms and Using CTCs for Monitoring Therapy Responses

Z. Hugh Fan, Ph.D., Professor, Mechanical and Aerospace Engineering, University of Florida

We will present our recent results on using microfluidic devices for enumerating circulating tumor cells (CTCs) in the blood samples of pancreatic cancer patients and using CTCs as a biomarker for monitoring the responses of cancer patients to anticancer therapy. Other platforms for CTC isolation and analysis will be reviewed and examined. Parameters for platform comparison will be discussed.

2:40 Diagnosis of Traumatic Brain Injury Using Machine Learning-Based miRNA Signatures in Nanomagnetically Isolated Brain-Derived Exosomes

Jin A. Ko, Ph.D. Candidate, Bioengineering and Electrical & Systems Engineering, University of Pennsylvania

Circulating exosomes contain molecular information, presenting an opportunity in diagnostics. While microfluidics can isolate cells from complex samples, scaling these approaches for exosomes is limited by low throughput and clogging of nanofluidics. Analysis of exosomes is confounded by heterogeneity between patients. We developed a device, wherein millions of nanofluidic channels operate in parallel, increasing throughput and eliminating clogging. We isolate exosomes from blood, profile their RNA cargo, and apply machine learning to generate a diagnosis.

3:10 Stabilization of Circulating Extracellular Vesicle Levels Using a Novel Blood Collection Tube

Nicholas George, Ph.D., Senior Research Scientist, Research and Development, Streck
Extracellular vesicles (EVs), including exosomes and microvesicles, harbor a multitude of cellular molecules and therefore reflect the activation status and identity of the parental cell.  Liquid biopsy protocols are expeditiously incorporating EVs as disease status biomarkers.  However, a significant obstacle in blood-based workflows is the instability of blood cells and increases in the concentration of non-disease EVs.  Here we describe utility of a blood collection tube intended for stabilizing draw-time concentrations of patient EVs.

3:40 Genomic Instability of Circulating Prostate Cancer CTCs
Sabine Mai, Ph.D., Senior Investigator, Manitoba Institute of Cell Biology/RIOH, Professor, University of Manitoba, Director, The Genomic Centre for Cancer Research and Diagnosis

4:10 Valentine’s Day Celebration in the Exhibit Hall with Poster Viewing

5:00 Breakout Discussions in the Exhibit Hall

These interactive discussion groups are open to all attendees, speakers, sponsors, & exhibitors. Participants choose a specific breakout discussion group to join. Each group has a moderator to ensure focused discussions around key issues within the topic. This format allows participants to meet potential collaborators, share examples from their work, vet ideas with peers, and be part of a group problem-solving endeavor. The discussions provide an informal exchange of ideas and are not meant to be a corporate or specific product discussion.

Challenges of Moving Liquid Biopsy Technologies/Assays Forward to Clinical Utility

Lynn R. Sorbara, Ph.D., Program Director, Cancer Biomarker Research Group, National Cancer Institute

Anthony Dickherber, Ph.D., Program Director, Center for Strategic Scientific Initiatives, National Cancer Institute

  • How can we tie together the clinical significance to detection of circulating nucleic acid markers and CTCs?
  • What are the major stumbling blocks?
    • IP issues? MTAs? CDAs?
    • Access to more or better tools?
    • Sample or patient accrual? Storage of biospecimens?
  • What are ways that we can enhance collaboration and exchange of information and data?

CTC Capture, Interrogation, and Culture

Richard J. Cote, M.D., FRCPath, FCAP, Professor, Joseph R. Coulter Jr. Chair, Pathology & Laboratory Medicine; Professor, Biochemistry and Molecular Biology; Chief of Pathology, Jackson Memorial Hospital

  • Live CTC capture
  • Conditions for expansion and propagation of CTC
  • Biomimetic Systems for CTC propagation
  • Novel interrogation of CTC

Tumor Tissue Extracellular Vesicles

Jan Lötvall, Ph.D., Professor, Krefting Research Centre, University of Gothenburg, Sweden, Chief Scientist, Codiak BioSciences, Cambridge, MA

  • Extracellular vesicle diversity
  • Isolation of extracellular vesicle subpopulations
  • Clinical validation of extracellular vesicle biomarkers
  • Multiplexing extracellular vesicle data

Liquid Biopsy for Brain Tumors

Brian V. Nahed, M.D., MSc, Associate Professor, Neurosurgery, Harvard Medical School; Associate Program Director, MGH

  • Brain tumor diagnosis, monitoring, and treatment
  • Blood tests / biomarkers
  • Mutational analysis of brain tumors and blood

6:00 Close of Day

Wednesday, February 14

7:30 am Registration Open and Morning Coffee

8:00 Plenary Keynote Session (click here for more details)

10:00 Refreshment Break and Poster Competition Winner Announced in the Exhibit Hall

ISOLATION OF VIABLE CTCS TO UNDERSTAND CTC BIOLOGY AND THERAPEUTIC TARGETS

10:50 Chairperson’s Remarks

Stuart S. Martin, Ph.D., Professor, Physiology, Marlene and Stewart Greenebaum NCI Comprehensive Cancer Center, University of Maryland School of Medicine

11:00 Can CTC Clusters Traverse Capillaries?

Sam H. Au, Ph.D., Lecturer, Department of Bioengineering, Imperial College London

Multicellular aggregates of circulating tumor cells (CTC clusters) are potent initiators of distant organ metastasis. However, it was assumed that CTC clusters are unable to pass through narrow vessels to reach these organs. Using fluid dynamic analyses and computational modelling, we explore the validity of this assumption through the use of microfluidic devices designed to mimic human capillary constrictions and animal models.

11:30 Capture, Interrogation and Culture of Viable CTC: Strategies for the Development of a Transformative Tool to Understand Cancer

Richard J. Cote, M.D., FRCPath, FCAP, Professor and Joseph R. Coulter Jr. Chair, Pathology & Laboratory Medicine; Professor, Biochemistry and Molecular Biology; Chief, Pathology, Jackson Memorial Hospital; Director, Dr. John T. Macdonald Foundation Biomedical Nanotechnology Institute

Circulating tumor cells (CTC) play a central role in tumor dissemination and metastases, are established as an important clinical biomarker for cancer diagnosis and prognosis and are key to unmasking insights into the metastatic process as well as discovering chemotherapeutic targets. We will discuss methods for capture of live CTC, which could lead to expansion, propagation, and creation of an important new biospecimen for cancer discovery.

12:00 pm Functional Analyses of CTCs in Cancer Patients

Catherine Alix-Panabières, Ph.D., Director, Laboratory of Rare Human Circulating Cells (LCCRH), Cellular and Tissular Biopathology of Cancers, University Medical Center of Montpellier

12:30 Session Break

12:40  Enjoy Lunch on Your Own


1:10 Dessert Break in the Exhibit Hall and Last Chance for Poster Viewing

DUAL ASSAYS

1:50 Chairperson’s Remarks

Shannon L. Stott, Ph.D., Assistant Professor, Department of Medicine, Massachusetts General Hospital, Harvard Medical School; BioMEMS Resource Center, The MGH Cancer Center

2:00 Liquid Biopsy for Brain Tumors

Brian V. Nahed, M.D., MSc, Associate Professor, Neurosurgery, Harvard Medical School; Associate Program Director; MGH Neurosurgery Residency, Massachusetts General Hospital

Despite advances in imaging, patients undergo surgery to establish a diagnosis followed by chemoradiation. Methods to monitor and detect response, recurrence, and distinguish it from post-treatment effects using magnetic resonance imaging are severely limited, and ultimately patients undergo additional surgery for diagnosis. Our laboratory has developed a microfluidic device to capture and analyze circulating tumor cells and extra-cellular vesicles which provides real-time mutational information about a patient’s brain tumor.

2:20 Extracellular Vesicles and Platelets: A Strong Friendship in CancerLand

Bakhos A. Tannous, Ph.D., Associate Professor of Neurology, Harvard Medical School; Director, Experimental Therapeutics and Molecular Imaging Lab; Director, Interdepartmental Neuroscience Center; Director, MGH Viral Vector Development Facility, Massachusetts General Hospital

Tumor-educated blood platelets (TEPs) are implicated as central players in the systemic and local responses to tumor growth, thereby altering their RNA profile. In this presentation, we will discuss the potential use of TEPs for pan-cancer, multiclass cancer, and companion diagnostics, enabling clinical advances in blood-based “liquid biopsies.” We will also discuss TEP-extracellular vesicles interactions and potential exchange of biomarker materials.

2:40 Tumor Tissue Extracellular Vesicles for Biomarker Discovery – RNA, DNA and Protein

Jan O. Lötvall, Ph.D., Professor, Krefting Research Centre, University of Gothenburg, Sweden; Chief Scientist, Codiak BioSciences

This presentation will discuss the diversity of extracellular vesicles, specifically in human tumor microenvironments. I will also introduce the concept of identifying and validating multiplex biomarker candidates, based on data acquired specifically from tumor tissue extracellular vesicles. The biomarker candidates are developed based on information on vesicle-associated cancer proteins, DNA and RNA.

3:00 PANEL DISCUSSION

3:30 Session Break

COMMERCIALIZING ISOLATION OF CTCs

3:40 PANEL DISCUSSION

Moderator: Anthony Dickherber, Ph.D., Program Director, National Cancer Institute’s (NCI) Office of the Director, Center for Strategic Scientific Initiatives, NIH

Panelists:

Patrizia Paterlini-Brechot, M.D., Ph.D., Founder, RARECELLS

Paul Smith, CEO, ANGLE Biosciences

Cha-Mei Tang, Sc.D., President and CEO, Creatv MicroTech, Inc.

  • Ease of use
  • Price point/low cost
  • Manufacturability
  • Scaling up production
  • Market outlook
  • Supply chain management

5:15 Close of Conference Program

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February 15-16, 2018


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