Cambridge Healthtech Institute’s Third Annual
Circulating Tumor Cells
Understanding Their Biology and Clinical Significance
August 20 - 21, 2018 | Grand Hyatt Washington | Washington, DC
Circulating tumor cells (CTC) have been in the spotlight during the last decade with many emerging technologies for CTC detection and isolation. However, despite their clearly demonstrated prognostic value, the complexity of their biology in relation to cancer progression and metastasis is still a challenge on the path to derive predictive information from CTCs. This year’s conference will gather many experts in the field to unravel the complexity of CTC biology including the heterogeneity and CTCs’ interactions with other immune cells. Advances in CTC technologies will also be showcased along with the clinical significance of CTC detection.
Final Agenda
Recommended Short Course*
SC1: Liquid Biopsy: Technology, Applications, Regulations and Reimbursement
Hatim Husain, MD, Physician, Medical Oncology, University of California, San Diego
John Simmons, PhD, Director, Translational Science & Diagnostics, Personal Genome Diagnostics
*Separate registration required
MONDAY, AUGUST 20
12:00 pm Main Conference Registration (Independence Foyer)
1:30 Chairperson’s Opening Remarks
Sunitha Nagrath, PhD, Associate Professor, Chemical Engineering, University of Michigan
1:40 New Tools for Liquid Biopsies: Microfluidics for the Efficient Isolation of Circulating Leukemia and Myeloma Cells
Steven A. Soper, PhD, Foundation Distinguished Professor, Chemistry, Mechanical Engineering, Cancer Biology, and Bioengineering, University of Kansas
We will discuss our work in negating the need for bone marrow biopsies by using liquid biopsies for leukemia and multiple myeloma by selecting circulating cells from whole blood to manage these diseases. Acute myeloid leukemia (AML) and pediatric acute lymphoblastic leukemia (ALL) minimum residual disease states were monitored for signs of recurrence using circulating leukemia cells. For multiple myeloma, circulating cells were used to stage patients (MGUS, smoldering or active myeloma).
2:10 Capture, Interrogation, Imaging, Automated Analysis and Culture of CTCs: Strategies for the Development of a Transformative Tool to Understand Cancer
Richard J. Cote, MD, FRCPath, FCAP, Professor, Joseph R. Coulter Jr. Chair, Pathology & Laboratory Medicine; Professor, Biochemistry and Molecular Biology; Chief of Pathology, Jackson Memorial Hospital
Circulating tumor cells (CTC) are important clinical biomarkers for cancer diagnosis, prognosis and target identification. Recently, we have described the presence of circulating Cancer Associated Fibroblasts (cCAF), which may have great importance. We will discuss integrated platforms for capture and novel imaging of CTC/cCAF, efforts to automate the analysis of CTC/cCAF images, and live CTC capture, which could lead to expansion, propagation, and creation of an important new biospecimen for cancer discovery.
2:40 Microfluidic Labyrinth Chip for Monitoring Cancer Stem Cells
Sunitha Nagrath, PhD, Associate Professor, Chemical Engineering, University of Michigan
We developed a novel chip containing fluid channels that uses hydrodynamic maze to separate circulating tumor cells into an analytic stream after sending blood samples through the chip. We are currently testing this microfluidic Labyrinth chip in a breast cancer clinical trial.
3:10 Overcoming the Challenges of Industrializing Microfluidic Devices: Liquid Biopsy & Large Volume Cell Separation Applications
Rolf Muller, PhD, CEO, BioFluidica Inc.
Georg Bauer, PhD, Senior Vice President, Development, STRATEC Consumables GmbH
BioFluidica, a diagnostic company has developed a ground-breaking platform for vastly improved cancer diagnostics from whole blood. Successful integration into the healthcare system for diagnostic of large patient cohorts requires a robust technology including scalable manufacturing. Injection molding of high-aspect ratio microchannels opens the path to scalable cell-based liquid biopsy.
3:25 An Open, End to End, and Flexible Platform for Scalable CTC collection, Identification, and Analysis
Tad George, PhD, Senior Director Scientific Applications, RareCyte, Inc.
RareCyte provides instrumentation and consumables that enable an exquisitely sensitive, accurate, simple, and repeatable workflow from liquid biopsy to single cell isolation. The open and end to end RareCyte CTC workflow will be the focus of this talk.
3:40 Networking Coffee Break (Independence Foyer)
4:15 pm Chairperson’s Remarks
Charles Mathews, Principal, ClearView Healthcare Partners
4:25 - 5:45 pm Global Dx Insights: Policy and Prediction for Diagnostics
Moderator: Cecilia Schott, PhD, Former Vice President, Precision Medicine, AstraZeneca
- Will value-based medicine replace fee-for-service?
- PAMA impact on reimbursement
- Changes in LDT oversight policy
- Changing landscape of IVD regulation in U.K. and Europe after Brexit
- What is the future of molecular diagnostics in medical care?
- How will these policy changes affect the patient?
Panelists:
Dennis J. Dietzen, PhD, DABCC, FAACC, President, AACC; Professor of Pathology & Immunology and Pediatrics, Washington University School of Medicine; Medical Director of Laboratory Services, St. Louis Children’s Hospital
John Leite, PhD, Vice President, Strategic Partnerships, Corporate and Business Development, Illumina
J. Leonard Lichtenfeld, MD, MACP, Deputy CMO, American Cancer Society, Inc.
Victoria M. Pratt, PhD, FACMG, Director, Pharmacogenomics and Molecular Genetics Laboratories, Department of Medical and Molecular Genetics, Indiana University School of Medicine (AMP President-Elect)
Susan Van Meter, Executive Director, AdvaMedDx
Ian S. Young, MD, PhD, Chief Scientific Advisor, Department of Health (Northern Ireland) and President, Association for Clinical Biochemistry and Laboratory Medicine (ACB), UK
5:45 Wine & Cheese Pairing Welcome Reception in the Exhibit Hall with Poster Viewing (Independence Ballroom)
7:00 Close of Day
TUESDAY, AUGUST 21
7:15 am Registration (Independence Foyer)
7:30 Problem Solving Breakout Sessions with Continental Breakfast (Independence F-I)
Liquid Biopsy to Advanced Personalized Care
Moderator: Massimo Cristofanilli, MD, FACP, Professor, Medicine; Associate Director, Translational Research and Precision Medicine; Director, OncoSET Precision Medicine Program, Medicine-Hematology and Oncology, Robert H Lurie Comprehensive Cancer Center, Feinberg School of Medicine
- CTCs and ctDNA are both important?
- CTCs commercial and technical challenges to clinical applications
- What is necessary in liquid biopsy field to become standard of care
CTC Capture, Interrogation, and Culture
Moderator: Richard J. Cote, MD, 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
- CTC and circulating tumor micro environment cells (cCAF)
- Novel image capture and analysis of CTC/cCAF
- Conditions for expansion and propagation of CTC
- Biomimetic Systems for CTC propagation
8:30 Chairperson’s Remarks
Sunitha Nagrath, PhD, Associate Professor, Chemical Engineering, University of Michigan
8:35 Microfluidics and CTCs: Detection, Metastatic Insights and Drug Testing
Siva A. Vanapalli, PhD, Professor, Chemical Engineering, Texas Tech University
Recent progress in cancer research has shown that circulating tumor cells (CTCs) can provide significant diagnostic and prognostic value. In this presentation, I will discuss advances we have made in our laboratory on microfluidic approaches for (i) label-free detection of tumor cells in blood, (ii) evaluating deformation and survival of CTCs to physical forces in circulation, and (iii) testing drugs in single tumor cells and clusters.
9:05 A Single-Step Assay for Rapid Detection of Circulating Tumor Cells
Youli Zu, MD, PhD, Professor and Endowed Chair in Pathology; Director, Hematopathology Section, Houston Methodist Hospital
By taking advantage of oligonucleotide aptamer technology, we have developed a single-step assay that is able to selectively highlight circulating tumor cells in whole blood samples for rapid detection in minutes.
9:35 Chairperson’s Remarks
Min Yu, MD, PhD, Assistant Professor, Stem Cell Biology and Regenerative Medicine Member, Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California
9:35 Molecular Signatures of Circulating Melanoma Cells for Monitoring Early Response to Immune Checkpoint Therapy
Xin Hong, PhD, Postdoc Fellow, Massachusetts General Hospital Cancer Center, Harvard Medical School
We applied digital RNA signatures of melanoma Circulating Tumor Cells (CTCs) to quantify early tumor response in patients treated with immune checkpoint inhibitors. A decrease in CTC-Score within 7 weeks of therapy correlates with improvement in progression-free survival (HR: 0.17, P=0.008) and overall survival (HR: 0.12, P=0.04). Thus, digital quantitation of melanoma CTCs enables serial noninvasive monitoring of tumor burden, supporting the rational application of immune checkpoint inhibition therapies.
10:05 Coffee Break in the Exhibit Hall with Poster Viewing (Independence Ballroom)
11:00 KEYNOTE PRESENTATION: Dissecting Liquid Biopsy in MBC: CTCs, ctDNA and CAMLs to Evaluate Innate Immunity
Franklin/McPherson
Massimo Cristofanilli, MD, FACP, Professor, Medicine; Associate Director, Translational Research and Precision Medicine; Director, OncoSET Precision Medicine Program, Medicine-Hematology and Oncology, Robert H. Lurie Comprehensive Cancer Center, Feinberg School of Medicine, Northwestern University
The detection of circulating tumor cells (CTCs) and clusters in MBC patients are prognostic and predict higher rate of metastatic spread. Furthermore, CTCs characterization combined with circulating cell-free DNA (ctDNA) provides a more comprehensive understanding of disease heterogeneity and advanced the possibility for performing a longitudinal molecular monitoring. Most recently, the discovery of CAMLs expanded the ability of blood-based diagnostics.
11:30 Using Liquid Biopsy to Detect Diverse Mechanisms of Resistance to Endocrine Therapy in Hormone-Receptor Positive Metastatic Breast Cancer
Costanza Paoletti, MD, Research Investigator, Internal Medicine, Hematology Oncology, University of Michigan Comprehensive Cancer Center
Liquid biopsies have allowed evaluation of cancer using serial, non-invasive approaches. Through circulating tumor cells’ assessment (enumeration, phenotyping, and next-generation sequencing), we were able to detect diverse mechanisms of resistance to endocrine therapy in hormone-receptor positive metastatic breast cancer. Overall, our data suggest that liquid biopsies may allow a better understanding of the bases of resistance to endocrine therapies revealing opportunity for precision medicine.
12:00 pm The Whole Transcriptional Landscape of Circulating Tumor Cells Compared to Metastases in Stage IV Breast Cancer
Julie Lang, MD, Associate Professor of Clinical Surgery Director, Breast Cancer Program, Surgery, University of Southern California, Norris Comprehensive Cancer Center
Metastatic breast cancer (MBC) and the circulating cells (CTCs) leading to macrometastasis are inherently different than primary breast cancer, evolving under the selection pressure of systemic therapy. A better understanding of the tumor biology of CTCs compared to metastasis may shed light on treatment opportunities. We present the transcriptomic landscape of CTCs with comparison to metastases and peripheral blood all acquired prior to treatment of newly diagnosed Stage IV breast cancer.
12:30 Luncheon Presentation (Sponsorship Opportunity Available) or Enjoy Lunch on Your Own
1:00 Refreshment and Cookie Break in the Exhibit Hall with Poster Viewing (Independence Ballroom)
1:30 Chairperson’s Remarks
Min Yu, MD, PhD, Assistant Professor, Stem Cell Biology and Regenerative Medicine Member, Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California
1:35 RNA-based Circulating Tumor Cell Signatures for Precision Cancer Medicine
David T. Miyamoto, MD, PhD, Assistant Professor, Radiation Oncology, Harvard Medical School, Center for Cancer Research, Massachusetts General Hospital
Circulating tumor cells (CTCs) are a form of “liquid biopsy” that can be performed non-invasively to predict and monitor treatment responses. In contrast to circulating tumor DNA (ctDNA), CTCs enable tumor RNA expression profiling, an analysis not possible with ctDNA. Microfluidic enrichment of CTCs followed by application of RNA-based digital PCR enables the high-throughput and highly specific detection of CTC molecular signatures in several cancer types. These CTC signatures can predict therapeutic responses and may enable the early detection of invasive cancers, thus guiding the precision management of cancer patients.
2:05 PANEL DISCUSSION: Defining Tumor Associated Circulating Cells - Moving toward Standardization and Clinical Utility
Moderator:
Lynn R. Sorbara, PhD, Program Director, Cancer Biomarker Research Group, National Cancer Institute
Panelists:
Sunitha Nagrath, PhD, Associate Professor, Chemical Engineering, University of Michigan
Richard J. Cote, MD, FRCPath, FCAP, Professor, Joseph R. Coulter Jr. Chair, Pathology & Laboratory Medicine; Professor, Biochemistry and Molecular Biology; Chief of Pathology, Jackson Memorial Hospital
Massimo Cristofanilli, MD, FACP, Professor, Medicine; Associate Director, Translational Research and Precision Medicine; Director, OncoSET Precision Medicine Program, Medicine-Hematology and Oncology, Robert H. Lurie Comprehensive Cancer Center, Feinberg School of Medicine, Northwestern University, Chicago
Youli Zu, MD, PhD, Professor and Endowed Chair in Pathology; Chief, Hematopathology Section; Director, Cancer Pathology Research Lab, Pathology and Genomic Medicine, Houston Methodist Hospital
Dario Marchetti, PhD, Director, Biomarker Research Program, Houston Methodist Research Institute Professor, Institute of Academic Medicine - Houston Methodist.
- Are we all speaking the same language? What is a CTC?
- What are the various types of tumor-associated circulating cells and tumor-associated circulating targets?
- What information can we glean from each cell type?
- What are the barriers for propagation and culture of CTC?
- What advances are needed to make the ease of CTC capture, analysis and interpretation easier, more reliable and more user-friendly?
- How can we address the challenge of clinical correlation with the detection of various tumor-associated circulating cells and other circulating targets?
- What strategies can we use to come to consensus on quality control and standardization for CTC characterization and analysis?
3:05 Circulating Tumor Cells: From the Research Bench to the CLIA Lab, a True Story
Madeline I. Repollet, PhD, CT(ASCP)CM, Head, Clinical Laboratories Operations and Services, Menarini Silicon Biosystems Labs
New diagnostic tests and innovative technologies are at the center of the process to streamline and personalize healthcare. Clinical laboratories hold the key to personalized medicine, and it is important to understand the impact of design and development of personalized medicine from the clinical lab perspective. The story of the CellSearch® CTC assay, the only FDA cleared test for circulating tumor cells, the first FDA cleared liquid biopsy, is an excellent example of this process.
3:35 Refreshment Break in the Exhibit Hall with Poster Viewing (Independence Ballroom)
4:20 Chairperson’s Remarks
Min Yu, MD, PhD, Assistant Professor, Stem Cell Biology and Regenerative Medicine Member, Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California
4:25 Circulating Stromal Cells Using CellSieve Microfilters - Expanding Clinical Utility of Blood Based Biopsy
Daniel Adams, Senior Research Scientist, Creatv MicroTech, Inc.
CellSieve™ microfiltration was the first blood based biopsy method used to identify and utilize Circulating Stromal Cells (CStCs) in parallel with CTCs. We introduce the concept of tumor associated circulating cells; describing their prevalence and profiles in the context of early detection, patient tracking and cancer pathogenesis; redefining our understanding of CTC identification and blood based diagnostics.
4:55 Microfluidic Isolation and Expansion of Patient-Derived Circulating Tumor Cells from Liquid Biopsies
Chwee Teck Lim, PhD, Professor, Mechanobiology Institute, National University of Singapore
We recently developed a simple but unique microfluidics-based culture approach that requires minimal preprocessing (30 min) and does not require prior enrichment of CTCs or depend on the use of growth factor supplements. The approach capitalizes on co-culture of immune cells from the same patient blood sample within specially designed microwells that promote CTC cluster formation within 2 weeks, with an overall cluster formation success rate of 50%. The described microfluidics system can be operated with a single syringe pump to introduce drug compounds (which takes 6 min), followed by incubation of the CTC clusters for 48 h before analysis. In addition to its applications in biomedical research, the rapid readout of our platform will enable clinicians to assess or predict a patient’s response to various therapeutic strategies to enable personalized or precision therapy.
5:25 Ex vivo Cultured CTCs Inform Mechanisms of Breast Cancer Metastasis
Min Yu, MD, PhD, 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 now demonstrate that different patient CTC lines have distinct metastatic tissue tropisms in immunodeficient mice and identified associated pathways to specific organs via RNA-seq and ATAC-seq analysis.
5:55 Defining the CTC Circulatory State: USP7 Targeting Identifies a Metastasis-Competent State within Bone Marrow-Resident Melanoma CTCs
Dario Marchetti, PhD, Director, Biomarker Research Program, Houston Methodist Research Institute Professor, Institute of Academic Medicine - Houston Methodist.
We used a negative depletion strategy to isolate Lin-neg cell population from the blood of metastatic melanoma patients. Biomarker gene expression profiling identified the presence of a discrete population of putative CTCs in Lin-neg cells, possessing upregulated gene transcripts implicated in cell survival and pro-development functions. We implanted Lin-neg/CTC-enriched population in NOD/SCID mice (CTC-derived xenografts or CDXs) and discovered divergent transcriptomic signatures of CDX-isolated bone marrow-resident tumor cells (BMRTCs) vs blood CTCs. Pathway analyses pointed to protein ubiquitination as the significantly altered canonical pathway associated with BMRTCs. The selective inhibition of USP7, a key deubiquinating enzyme of this pathway, lead to a significant reduction of CDX organ micro-metastasis. Together, these results provide first-time evidence of a functionally relevant CTC phenotype within patient-derived, BM-resident melanoma CTCs contributing to disease progression; and support further investigation of USP7 inhibitors in new strategies to prevent overt or undetectable metastasis.
6:25 End of Circulating Tumor Cells
6:00 Dinner Short Course Registration (Independence Foyer)
6:45 - 9:15 pm Recommended Dinner Short Course*
SC8: Commercialization Boot Camp: Manual for Success in Molecular Diagnostics
Harry Glorikian, Healthcare Consultant
Stan Skrzypczak, Vice President, Corporate Development and Reimbursement, Guardant Health, Inc.
*Separate registration required