Cambridge Healthtech Institute’s Fifth Annual

Circulating Tumor Cells

Future of Cancer Management

February 16-18, 2015 | Moscone North Convention Center | San Francisco, CA
Part of the 22nd Annual Molecular Medicine Tri-Conference

 

Circulating biomarkers continue to dominate cancer research by detecting the elusive signature in blood, serum or plasma. Isolation and characterization of circulating tumor cells and cell-free DNA enable the precise diagnosis and monitoring of cancer but significant challenges remain in validating methods for clinical use. This conference will showcase advances in technology and clinical applications and ultimately decide which will be the most robust technologies for personalized cancer care.

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., William H. Pryor Emeritus Professor, Biomedical Engineering and Chemistry, University of North Carolina, Chapel Hill

Avraham Rasooly, Ph.D., Health Scientist Administrator, Cancer Diagnosis Program, National Cancer Institute


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Monday, February 16

10:30 am Conference Program Registration


KEYNOTE SESSION: MARKER OF CHOICE FOR CLINICAL USE.

11:50 Chairperson’s Opening Remarks

Stefanie Jeffrey, M.D., John and Marva Warnock Professor, Surgery; Chief of Surgical Oncology Research, Stanford University School of Medicine and Klaus Pantel, M.D., Professor and Founding Director, Institute of Tumor Biology, University, Medical Center Hamburg-Eppendorf, University of Hamburg

12:00 pm CTC: Current Clinical Utility and Future Prospects

Daniel F. Hayes, M.D., FASCO, Stuart B. Padnos Professor, Breast Cancer Research; Clinical Director, Breast Oncology Program, Internal Medicine and Hematology Oncology, University of Michigan Comprehensive Cancer Center

CTC enumeration is clearly associated with poor prognosis in several epithelial malignancies. A prospective randomized clinical trial in metastatic breast cancer (S0500) demonstrated that failure to clear CTC harbors a terrible prognosis, but that switching to a different chemotherapy is of no value. Future studies will focus on molecular characterization of CTC and investigating genomic, targeted therapies based on these results.

12:30 Qualifying Blood-Based Molecular Assays for Targeted Therapies in Cancer

Daniel C. Danila, M.D., Assistant Attending, Medicine, Memorial Sloan Kettering Cancer Center

Unmet needs in cancer drug development and patient management are the ability to monitor treatment benefit and to identify the target of interest in a tumor at the time treatment is being considered. Given the effort and cost to new blood biomarkers, it is essential to develop metrics to determine which promising assays warrant prospective testing in large-scale phase III trials to establish qualification in the context of use.

1:00 Session Break


1:15 Luncheon Presentation I: High Sensitive Detection of Circulating Tumor Cells Including EMT-CTCs in NSCLC Patients by TelomeScan F35

Shinsaku Togo, MD, Ph.D., Associate Professor, Division of Respiratory Medicine, Juntendo University Faculty of Medicine & Graduate School of Medicine

We established a unique CTC-detecting platform using TelomeScan F35, a telomerase-specific replication-selective adenovirus expressing GFP. In clinical feasibility studies, we demonstrated that TelomeScan F35 is useful to detect alive and EMT-induced CTCs from patients of various types of cancer. In NSCLC, CTCs were sensitively detected from patients with early clinical stage (Stage I) and it suggests TelomeScan F35 is a powerful surrogate indicator and liquid biopsy for cancer diagnosis.

Leica Biosystems 1:45 Luncheon Presentation II

Speaker to be Announced

2:15 Session Break


CHARACTERIZING CTCs 

2:30 Chairperson’s Remarks

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

2:40 Circulating Tumor Cells in Lung Cancer, Biomarkers, Biology, and Mouse Models

Caroline Dive, B.Pharm, Ph.D., Professor & Senior Group Leader, Clinical and Experimental Pharmacology Group, Cancer Research UK Manchester Institute

Dr. Dive will discuss the current utility of CTCs in lung cancer in early clinical trials and the challenges associated with use of new marker independent CTC enrichment platforms in clinical trial samples. She will also focus on the development of patient derived CTC explant models that now offer unique opportunities to study lung cancer biology, discover new drug targets, understand drug resistance mechanisms and test novel therapies.

3:10 Novel Approaches to Enable Molecular Characterization of CTCs

Nikolas H. Stoecklein, M.D., Professor, General Visceral and Pediatric Surgery, University Hospital of the Heinrich-Heine, University of Düsseldorf

The talk will cover a recently established workflow to enable high-resolution genomic analysis of single CTCs and will discuss the concept of diagnostic leukapheresis (DLA) to increase the detection rate of CTCs by screening larger blood volumes.

3:40 Deep Sequencing of Circulating Tumor Cells as a Window into Disseminated Cancer

Jens Lohr, M.D., Ph.D., Instructor in Medicine, Medical Oncology, Cancer Program, Dana-Farber Cancer Institute; Broad Institute

We have developed targeted and whole exome sequencing frameworks to explore the genomics of circulating tumor cells (CTCs), with a focus on defining somatic mutations in single CTCs. We are investigating how the genetics of CTCs evolve over time and how they compare to primary tumors and metastases.

4:10 Characterization and Molecular Profiling of CTCs using DEPArray™ and Ampli1™ Technologies

Farideh Z. Bischoff, Ph.D., Executive Director, Scientific Affairs, Silicon Biosystems
DEPArray™ allows sorting and recovery of target cells using image-based identification of specific markers.   Enriched cell suspensions can be used to recover rare cells with 100% purity. Using this
approach, CTCs have been successfully recovered for downstream molecular profiling and NGS.
 

Rarecells4:25 Sponsored Presentation

Speaker to be Announced

4:40 Break and Transition to Plenary Session

5:00 Plenary Session

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

7:30 Close of Day


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Tuesday, February 17

7:00 am Registration and Morning Coffee

8:00 Plenary Session

Slone Partners9:00 Refreshment Break in the Exhibit Hall with Poster Viewing


CELLS VS. CIRCULATING BIOMARKERs

10:05 Chairperson’s Remarks

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

10:15 Platforms for CTC Isolation and Analysis

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

We will present our recent results on integrating aptamers, antibodies, nanoparticles, and multivalent binding mechanisms with microfluidics for the isolation of cancer cells, as well as on the correlation between CTC enumeration and therapy responses of pancreatic cancer patients. Other platforms for CTC isolation and analysis will be reviewed and examined. Parameters for platform comparison will be discussed.

10:45 Circulating Tumor DNA:  Opportunities and Challenges on the Road to Clinical Utility

Mark Lee, M.D., Ph.D., Google[x] Life Sciences

The advent of new technologies for sensitive and specific detection of cell-free, circulating tumor DNA (ctDNA) in plasma has generated considerable enthusiasm for this new class of biomarkers to improve clinical decision-making in oncology.  Emerging evidence suggests a number of promising potential clinical applications.   Considerations and strategies to establish clinical utility of ctDNA will be discussed.

11:15 Biology and Function of Exosomes

Raghu Kalluri, M.D., Ph.D., Professor & Chair, Cancer Biology, MD Anderson Cancer Center

The lecture will discuss the biology and function of exosomes in cancer detection and progression of cancer. DNA, RNA and protein profiles will be discussed with specific emphasis on early detection of cancer.

11:45 Microfluidic Isolation of Microvesicles and Circulating Tumor Cells from Cancer Patients

Shannon L. Stott, Ph.D., Assistant Professor, Medicine, Massachusetts General Hospital and Harvard Medical School

Circulating tumor cells (CTCs) and microvesicles (MVs) are found in the bloodstream of cancer patients and have the potential to help guide cancer treatment. Through a collaborative effort between bioengineers, biologists, and clinicians, our group at MGH has developed microfluidic devices to isolate these rare circulating biomarkers from whole blood. I will describe our recent efforts to molecularly characterize CTCs and MVs, and the insights gained from our analysis.

12:15 pm Session Break

12:25 Luncheon Presentation I: Circulating Tumor Cells: From Enumeration to Comprehensive Characterization

Nicholas C. Dracopoli, Ph.D., Vice President, Oncology Translational Research, Janssen R&D, Johnson & Johnson

This presentation will describe a novel platform for the capture and analysis of circulating tumor cells (CTC). The platform is antibody independent and delivers viable CTCs in suspension. This novel platform enables routine enumeration of all tumor derived cells, ex vivo propagation of the CTCs, and comprehensive molecular and protein analyses using single cell analytical methods to characterize tissue of origin, epithelial-mesenchymal transition, stem cells and functional biomarkers.

12:55 Luncheon Presentation II (Sponsorship Opportunity Available)

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


BEYOND SELECTION: Single Cell Analysis on CTCs 

2:00 Chairperson’s Remarks

Steven A. Soper, Ph.D.

2:10 Drug-Induced Damage of Genomic DNA Harvested from Circulating Tumor Cell Sub-Populations

Steven A. Soper, Ph.D., William H. Pryor Emeritus Professor, Biomedical Engineering and Chemistry, University of North Carolina, Chapel Hill

An innovative assay combined with groundbreaking hardware for the isolation and processing of distinct sub-populations of circulating tumor cells (CTCs) for a patient’s cancer will be discussed. The assay quantifies response to therapy using three pieces of information for different CTC sub-populations; (1) CTC number; (2) CTC viability; and (3) frequency of DNA abasic (AP) sites in the CTCs’ genomic DNA.

2:40 Isolation and Downstream Analysis of Circulating Tumor Cells

Daniel T. Chiu, Ph.D., A. Bruce Montgomery Professor, Chemistry & Bioengineering, University of Washington, Seattle

This presentation will describe advances we have made with the eDAR platform for the isolation of rare cells, with emphasis on employing eDAR for the downstream analysis of circulating tumor cells.

3:10 Single-Cell Analysis Using Drop Based Microfluidics

David A. Weitz, Ph.D., Mallinckrodt Professor, Physics, School of Engineering & Applied Sciences, Harvard University

Drop-based microfluidics have enabled large numbers of cells to be encapsulated in individual drops, a few picoliters in volume, immersed in an inert carrier oil. Each drop can be precisely controlled and analyzed, enabling large numbers of cells to be screened and specific cells identified for further analysis using either PCR or next generation sequencing. This technology has great potential for studies of circulating tumor cells.

3:40 Isolation and Identification of Circulating Trophoblastic Cells in Maternal Blood 

François Forestier, Ph.D., Professor, Haematology, University Paris 11, ScreenCell

Among fetal cells that cross the placenta, trophoblastic cells are of great interest, because they can be used to replace invasive prenatal diagnosis by a non-invasive test, by capture and cell culture. Cells are isolated from maternal blood by size selection using ScreenCell® CC device. This procedure enables selection of living trophoblastic cells. Specific culture conditions have been developed to expand isolated trophoblastic cells, to obtain enough material to perform downstream analyses.

4:10 Mardi Gras Celebration in the Exhibit Hall with Poster Viewing

5:00 Breakout Discussions in the Exhibit Hall

This interactive session provides attendees an opportunity to choose a specific 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.

New Technologies for CTC Analyses: Is Selection and Enumeration Sufficient

Steven A. Soper, Ph.D., William H. Pryor Emeritus Professor, Biomedical Engineering and Chemistry, University of North Carolina, Chapel Hill

• What are follow up assays that are clinically relevant for cancer disease management that can be secured from CTCs?
• What are the advantages of using CTCs for various follow up assays compared to tumor tissue?
• What are the important metrics for the use of CTCs in these assays?
• New CTC selection technologies; how should they be integrated to follow up assays?
 

Understanding the Positive and Negative Effects of Chemotherapies on Circulating Tumor Cells

Stuart S. Martin, Ph.D., Associate Professor, Physiology, Greenebaum Cancer Center, University of Maryland School of Medicine

• Surgery and chemotherapy can increase CTCs
• Treatments that reduce CTCs can improve patient outcome
• Treatments that increase CTCs can increase relapse risk
• Chemotherapies can increase stem cell characteristics and microtentacles
 

6:00 Close of Day


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Wednesday, February 18

7:00 am Breakfast Presentation (Sponsorship Opportunity Available) or Morning Coffee

8:00 Plenary Session Panel

9:45 Refreshment Break and Poster Competition Winner Announced in the Exhibit Hall


TECHNOLOGY STRIDES FOR CTCs 

10:35 Chairperson’s Remarks

Avraham Rasooly, Ph.D., Health Scientist Administrator, Division of Cancer Treatment and Diagnosis, National Cancer Institute

10:45 Vortex Technology for CTC Collection and Automated Image Cytometry for CTC Detection

Dino Di Carlo, Ph.D., Associate Professor, Bioengineering, California NanoSystems Institute, Jonsson Comprehensive Cancer Center, University of California, Los Angeles

Dr. Di Carlo will introduce the vortex cell isolation and concentration technology and discuss the latest results in isolating and characterizing circulating tumor cells using label-free imaging approaches.

11:15 Nanoroughened Surfaces for Efficient Capture of Circulating Tumor Cells without Using Capture Antibodies

Jianping Fu, Ph.D., Mechanical Engineering & Biomedical Engineering, University of Michigan, Ann Arbor

Circulating tumor cells (CTCs) detached from both primary and metastatic lesions represent a potential alternative to invasive biopsies as a source of tumor tissue for the detection, characterization and monitoring of cancers. Here we report a simple yet effective strategy for capturing CTCs without using capture antibodies. Our method uniquely utilized the differential adhesion preference of cancer cells to nanorough surfaces when compared to normal blood cells and thus did not depend on their physical size or surface protein expression, a significant advantage compared to other techniques.

11:45 Geometrically Enhanced Differential Immunocapture (GEDI): Informing Surgical and Medical Cancer Treatment via Capture of Circulating Tumor Cells

Brian J. Kirby, Ph.D., Associate Professor, Mechanical and Aerospace Engineering, Cornell University

We will present results for early-stage circulating cell capture and its use to stage surgical decisions, as well as late-stage circulating tumor cell capture and its use to inform choice of chemotherapy. CTC capture is performed with Geometrically Enhance Differential Immunocapture, a microfluidic systems that uses both immunocapture and size-based cell trajectories to optimize efficiency and purity.

12:15 pm Session Break

12:25 Luncheon Presentation (Sponsorship Opportunity Available) or Lunch on Your Own

1:00 Refreshment Break in the Exhibit Hall and Last Chance for Poster Viewing


CLINICAL USE OF CTCs 

1:40 Chairperson’s Remarks

Avraham Rasooly, Ph.D., Health Scientist Administrator, Division of Cancer Treatment and Diagnosis, National Cancer Institute

1:50 Detection and Molecular Characterization of CTCs in Glioma Patients

Klaus Pantel, M.D., Professor & Chairman, Tumor Biology, University Medical Center Hamburg-Eppendorf

Glioblastoma multiform (GBM) is the most frequent and aggressive brain tumor in adults. The dogma that GBM spread is restricted to the brain was challenged by reports on extracranial metastases after organ transplantation from GBM donors. The CTC detection approach developed in this study is easily applicable as a companion diagnostic to identify patients with extracranial tumor cell spread, and it might be advisable to exclude these patients as organ donors.

2:20 Single Cell Genomic Analyses of Circulating Tumor Cells

Sunney Xie, Ph.D., Mallinckrodt Professor, Chemistry and Chemical Biology, Harvard University

We have demonstrated whole genome sequencing of circulating tumor cells (CTCs) with multiple annealing and looping-based amplification cycles (MALBAC). We discovered that CTCs of the same patient exhibit reproducible CNV gain and loss patterns, which are similar to the patterns of metastatic sites. Patients with the same cancer type have similar patterns while patients with different cancers have dissimilar patterns. The fact that CTC’s CNV patterns are tissue and cancer dependent offers prospects for noninvasive cancer diagnostics.

2:50 Targeting Microtentacles on Circulating Tumor Cells to Reduce Metastasis

Stuart S. Martin, Ph.D., Associate Professor, Physiology, Greenebaum Cancer Center, University of Maryland School of Medicine

Tumor cells generate dynamic membrane microtentacles (McTNs) in free-floating microenvironments, that promote the reattachment of circulating tumor cells in distant tissues. These McTNs arise from imbalances between microtubule extension and contraction of the actin cortex, and are detectable in freshly-isolated tumor cells from patients. By defining the cytoskeletal mechanisms underlying McTNs, we are clarifying how existing chemotherapies affect CTCs and identifying new therapeutic opportunities..

3:20 Sponsored Presentations (Opportunities Available)

3:50 Refreshment Break


CTCs FOR COMPANION DIAGNOSTICs

4:00 Chairperson’s Remarks

Steven A. Soper, Ph.D., William H. Pryor Emeritus Professor, Biomedical Engineering and Chemistry, University of North Carolina, Chapel Hill

4:10 CTCs in Mouse Models

Jen Jen Yeh, M.D., Associate Professor, Surgery and Pharmacology, UNC Chapel Hill Lineberger Comprehensive Cancer Center

This presentation will provide an overview of the data on CTCs in mouse models and their possible uses as biomarkers.

4:40 Challenges and Opportunities in the Use of CTCs for Companion Diagnostic Development

Elizabeth Punnoose, Ph.D., Senior Scientist, Oncology Biomarker Development, Genentech, Inc.

Circulating tumor cells offer promise as a surrogate source of cancer cells that can be obtained in real time and may provide opportunities to evaluate predictive biomarkers that can guide treatment decisions. In this review, we consider some of the technical hurdles around CTC numbers and suitability of various CTC capture and analysis platforms for biomarker evaluation. In addition, we consider the potential regulatory hurdles to development of CTC-based diagnostics. Finally, we suggest a path for co-development of anticancer therapeutics with CTC-based diagnostics that could enable clinical validation and qualification of CTC-based assays as companion diagnostics.

5:10 Circulating Tumor Cells: What Is in It for the Patient? A Vision Towards the Future

Paul A. van de Wiel, Ph.D., Senior Director, Precision and Decentralized Diagnostics, Philips Research

Knowledge on signal transduction pathways as drivers of cancer growth has fuelled development of targeted therapy. However, good companion diagnostic tests to determine the tumor driving pathways are still lacking. We will discuss novel approaches of assessing active tumor pathways based on advanced staining of CTCs in combination with automated image interpretation on a digital pathology platform, and by PCR-based analysis of isolated CTCs.

5:40 Close of Conference Program



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