Circulating tumor cells and cell-free tumor DNA have dominated the headlines for the past decade and presently new liquid biopsy tests are entering the clinic. These will enable improved diagnosis of cancer, early detection, and a new era of companion
diagnostics for therapy selection, monitoring, predicting outcomes, and measuring the risk of recurrence. New tools include methods to both isolate CTCs and destroy them with lasers, digital microfluidics, and epigenetic measurement to better diagnose,
prognose, and treat disease.
Final Agenda
Scientific Advisory Board
Catherine Alix-Panabières, PhD, Director, Laboratory of Rare Human Circulating Cells (LCCRH), Pathology and Onco-Biology Department, University Medical Center of Montpellier
Stefanie Jeffrey, MD, John and Marva Warnock Professor, Surgery;
Chief, Surgical Oncology Research, Stanford University School of Medicine
Stuart S. Martin, PhD, Professor, Physiology, Marlene and Stewart Greenebaum NCI Comprehensive Cancer Center, University of Maryland School of Medicine
Klaus Pantel,
MD, Professor and Founding Director, Institute of Tumor Biology, University, Medical Center Hamburg-Eppendorf
Steven A. Soper, PhD, Professor, Micro and Nanofabricated Tools for Biological Discovery and Medical Diagnostics, University of Kansas
Shannon L. Stott, PhD, Assistant Professor, Department of Medicine, Massachusetts General Hospital, Harvard Medical School; BioMEMS Resource Center, The MGH Cancer Center
Monday, March 2
10:30 Conference Program Registration Open
11:45 Organizer’s Opening Remarks
Christina Lingham, Executive Director, Conferences and Fellow, Cambridge Healthtech Institute
11:50 Chairperson’s Remarks
Klaus Pantel, MD, Professor and Founding Director, Institute of Tumor Biology, University Medical Center Hamburg-Eppendorf
11:55 Implementation of Liquid Biopsies in Clinical Trials – Promise, Progress, and Pitfalls
Ralph Graeser, PhD, Senior Translational Medicine Expert, Boehringer Ingelheim Pharma GmbH
This talk will discuss the use of liquid biopsies in the clinic, and whether it is diagnostic, prognostic, or predictive, as well as CTCs vs. ctDNA: one or the other – or both? We will explore CANCER-id – a public-private partnership with
the goal to clinically validate liquid biopsies, and BI in CANCER-ID: CTCs in NSCLC, and why there are so few.
12:25 pm CTCs and Their Value in a Multimodality Liquid Biopsy Analysis
Markus Sprenger-Haussels, PhD, Senior Director, Head of Sample Technologies Product Development Life Sciences, QIAGEN GmbH
Initial liquid biopsy research studies focused on correlation of single analytes, such as CTC epitopes, ctDNA mutations or exosomal RNA expression with clinical prognosis, therapy stratification, or disease monitoring. The field of liquid biopsy is developing
toward a multi-analyte approach that better reflects cancer’s complexity and provides more comprehensive information. In the future, even more insights are promised by inclusion of transcriptional and genetic CTC profiles into the multimodal
liquid biopsies analysis.
12:55 Session Break
1:05 LUNCHEON PRESENTATION: Advancing Liquid Biopsy
Mark Connelly, Chief Industrial Operations and R&D Officer, Menarini Silicon Biosystems
1:35 Luncheon Presentation II (Sponsorship Opportunity Available)
2:05 Session Break
2:20 Chairperson’s Remarks
Shannon L. Stott, PhD, Assistant Professor, Department of Medicine, Massachusetts General Hospital, Harvard Medical School; BioMEMS Resource Center, The MGH Cancer Center
2:25 Molecular Signatures of Circulating Melanoma Cells for Monitoring Early Response to Immune Checkpoint Therapy
Ryan J. Sullivan, MD, Associate Director, Melanoma Program, MGH Cancer Center
To optimize immunotherapy treatment selection for patients with metastatic melanoma, predictive biomarkers are needed. We aimed to develop an assay that could detect and monitor circulating tumor cells in patients with melanoma. To determine the clinical
utility of this assay, we serially assayed patients treated with immune checkpoint inhibitor therapy, generated a “CTC-score” for each time-point, and correlated changes in the assay over time with efficacy.
2:55 APOBEC Mutagenesis: A Tactic and a Vulnerability of Cancer
Michael S. Lawrence, PhD, Assistant Professor of Pathology, Harvard Medical School; Assistant Geneticist, Massachusetts General Hospital Cancer Center
APOBEC enzymes mutate the DNA of cancer cells, especially in the context of targeted therapy, where they help speed the search of sequence space for resistance mutations. However, APOBEC overactivity also causes replication stress and renders cancer cells
vulnerable to synthetic lethality with inhibitors of DNA damage sensing. Moreover, accumulation of APOBEC-derived neoantigens may predict increased response to immunotherapy. New understanding of APOBEC’s favored genomic targets enables sensitive
detection of APOBEC activity in tumors and CTCs.
3:25 SBS-CTC Platform for Early Breast Cancer Diagnosis
Roberta
Carbone, PhD, Bio-Lab, Tethis S.p.A
CTC based diagnostic for cancer suffers from standardization, sensitivity and specificity, mainly in early cancer settings. SBS-CTC platform, from blood sample to single cells, provides a solution for liquid biopsy prepared at point of blood collection
for provide clinical sample integrity. Pilot study in a cohort of 60 pT1-T2 early breast cancer patients will be presented to provide unprecedented evidences of the high sensitivity and versatility of SBS-CTC platform in early cancer diagnostics.
3:55 High Sensitivity and Scalability Technology for Large Cohort Liquid Biopsy Applications
Rolf Muller, CEO, BioFluidica
Biofluidica’s microfluidics-based systems are designed for high sensitivity and specificity to discover and isolate live diagnostically relevant target cells. The isolation chips are mass produced through injection molding processes from materials
designed to be easily manufactured bringing a solid, scalable supply chain for cell-based analysis to large cohort studies.
4:10 A Clinically Actionable Liquid Biopsy End-to-End Platform for Metastatic Solid Tumors
Melissa McConechy, PhD, Senior Manager, Assay Development, Research and Development, Contextual Genomics
Use of liquid biopsy is quickly becoming part of personalized medicine approaches. In this talk, we will present a new end-to-end liquid biopsy platform, FOLLOW IT, that empowers clinical laboratories with the tools to perform in-house testing. Current
studies for targeted treatment selection and disease monitoring will be discussed.
4:25 Refreshment Break and Transition to Plenary Keynote
4:35 Welcome Remarks
Cindy Crowninshield, RDN, LDN, HHC, Executive Event Director, Cambridge Healthtech Institute
4:45 PLENARY KEYNOTE INTRODUCTION
Thomas Westerling-Bui, PhD, Senior Scientist, Regional Business Development, Aiforia
5:00 PLENARY KEYNOTE PRESENTATION: High-Performance Medicine
Eric Topol, MD, Founder and Director, Scripps Research Translational Institute (SRTI); Author, Deep Medicine: How Artificial
Intelligence Can Make Healthcare Human Again
6:00 Grand Opening Reception in the Exhibit Hall with Poster Viewing, Speed Networking, Book Signing, and Meetup Group
7:30 End of Day
Tuesday, March 3
7:30 am Registration Open and Morning Coffee
8:00 Organizer’s Remarks
Christina Lingham, Executive Director, Conferences and Fellow, Cambridge Healthtech Institute
8:05 Chairpersons’ Remarks
Stefanie Jeffrey, MD, John and Marva Warnock Professor, Surgery; Chief, Surgical Oncology Research, Stanford University School of Medicine
Ash Alizadeh, PhD, Associate Professor of Medicine, Divisions of Oncology & Hematology, Stanford University School of Medicine
8:10 The Use of Epigenetic Alterations for Measuring ctDNA
Scott V. Bratman, MD, PhD, Radiation Oncologist, Radiation Medicine Program; Scientist, Princess Margaret Cancer Centre, University Health Network; Assistant Professor, Departments of Radiation Oncology and Medical Biophysics, University of
Toronto
Mutation-based ctDNA assays are increasingly utilized in the clinic as liquid biopsies. For certain oncology applications, however, mutation-based liquid biopsy approaches have inherent limitations that are difficult to overcome with existing techniques.
Alternative approaches include the detection of various epigenetic alterations within cell-free DNA. For instance, DNA methylation and hydroxymethylation are emerging as measurable features that are also amenable to use as liquid biopsies. This
presentation will review the current landscape of epigenetic-based ctDNA assays and their potential impact on oncology. Technical challenges to measuring epigenetic alterations in cell-free DNA will also be discussed.
8:40 Whole Blood Stabilization for Liquid Biopsy
Shannon L. Stott, PhD, Assistant Professor, Department of Medicine, Massachusetts General Hospital, Harvard Medical School; BioMEMS Resource Center, The MGH Cancer Center
Clinical translation of various liquid biopsy assays is critically dependent on the stability and hence repeatability of the blood specimens. Currently, chemical fixation remains the only FDA-cleared stabilization method for circulating tumor cell
(CTC) isolation. While this method enables CTC enumeration, fixation severely degrades RNA and prohibits detailed molecular analysis which is invaluable in understanding disease progression and drug resistance mechanisms. The need to preserve
blood in its viable state is exemplified by the very fact that rare-cell technologies require precisely engineered devices which are highly sensitive to minor degradations in blood cell quality. Our group challenges the current dogma that whole
blood can only be held at room temperature for up to several hours prior to processing. In this talk, I will share our data that utilizes hypothermic preservation to extend the viability of whole blood cells. I will highlight the non-fixative
nature of our approach and demonstrate its critical advantage in preserving RNA integrity for up to 72 hours.
9:10 Liquid Biopsy-Based Biomarkers for Cancer Immunotherapy: Opportunities and Challenges
Sam Hanash, MD, PhD, Director, McCombs Institute for Cancer Detection and Treatment, University of Texas MD Anderson Cancer Center
Multiple circulating biomarkers that have the potential to serve as predictive prognostic biomarkers to guide cancer immunotherapy are currently being pursued. These include tumor-derived microvesicles, soluble immune proteins, and metabolites. The
current opportunities and challenges will be presented.
9:40 Refreshment Break in the Exhibit Hall with Poster Viewing, Speed Networking, Book Signing, and Meetup Group
10:40 Saliva Liquid Biopsy (SLB)
David T.W. Wong, DMD, DMSc, Associate Dean of Research and Felix & Mildred Yip Endowed Distinguished Professor, UCLA School of Dentistry
Saliva harbors multiple -omics constituents that can be harnessed non-invasively for liquid biopsy applications. PCR-based technologies cannot detect ctDNA in saliva samples, whereas an emerging liquid biopsy platform, EFIRM, can consistently detect
ctDNA from NSCLC patients, plasma, and saliva, with concordance of 95%+ with biopsy-based genotyping. EFIRM detects ctDNA with a minimal footprint of 30bp, LOD of single-digit copy number, and conductance sensitivity inversely proportional to
ctDNA fragment size.
11:10 Panel Discussion with Session Speakers
11:40 Introducing RNA Complete BCT (RUO), a Novel Blood Collection Tube Targeting Circulating RNA and Extracellular Vesicles
Nicholas George, PhD, Research & Development, Scientific Manager, Research and Development, Streck
Liquid Biopsy assays exploiting EVs and cfRNA provide a comprehensive and dynamic view of the disease state. Here we describe the Streck RNA Complete BCT and its incorporation into the Liquid Biopsy workflow allowing for delayed sample processing
without effect on sample integrity or downstream analyte analysis in research applications.
11:55 Limitations and New Methods in the Characterization of Microfluidic Devices for Manufacturing QC
Georg Bauer, Business Manager, STRATEC Consumables GmbH
As the momentum for microfluidic devices in Liquid Biopsy continues to grow, the implementation of effective QC for manufacturing processes is gaining importance. A number of startup companies as well as major diagnostic and biopharma companies are
developing microfluidic devices for the sample prep.
12:10 pm Session Break
12:20 Luncheon Presentation I to be Announced
12:50 Luncheon Presentation II (Sponsorship Opportunity Available)
1:20 Refreshment Break in the Exhibit Hall with Poster Viewing, Speed Networking, Book Signing, and Meetup Group
2:00 Breakout Discussions in the Exhibit Hall (please click here for details)
3:00 Transition to Keynote Session
3:15 Organizer’s Remarks
Christina Lingham, Executive Director, Conferences and Fellow, Cambridge Healthtech Institute
3:20 Keynote Introduction
Allison Mallory, PhD, Director, R&D Molecular Biology, Stilla Technologies
3:35 What Does the New Era of Genomic Medicine Look Like? Effects on Patient Care, Therapeutics, and Diagnostics
20 years after the completion of the first draft of the Human Genome Project, there is compelling evidence of genomics delivering the rich promise of precision medicine. There have been major advances in the throughput and affordability of genome
sequencing, enhanced tools for genome analysis and interpretation, new paradigms for therapeutics and strong signs of clinical benefit using genome editing. But major challenges remain. In this special plenary roundtable, three established pioneers
of genomic medicine – David Haussler, Stephen Kingsmore, and Liz Worthey – offer their insights on the extraordinary advances in genomic medicine over the past 1-2 decades and share their hopes and concerns for the future of our field.
Moderator: Kevin
Davies, PhD, Executive Editor, The CRISPR Journal, Mary Ann Liebert, Inc.
Panelists: Stephen Kingsmore, MD, DSc, President/CEO, Rady Children’s Institute for Genomic Medicine
David Haussler, PhD, Investigator, Howard Hughes Medical Institute; Distinguished Professor, Biomolecular Engineering, University of California, Santa Cruz; Scientific Director, UC Santa Cruz Genomics Institute; Scientific Co-Director, California
Institute for Quantitative Biosciences (QB3)
Elizabeth Worthey, PhD, Director, Genomic Medicine, University of Alabama, Birmingham School of Medicine
4:50 Spring Fling Celebration in the Exhibit Hall with Poster Viewing, Speed Networking, Book Signing, and Meetup Group
6:00 End of Day
Wednesday, March 4
6:45 am Registration Open
7:00 BREAKFAST PANEL DISCUSSION: The Time is NOW: Creating Meaningful Change for Women in the Workplace (Sponsorship Opportunity Available)
(please see Women in Science page for details)
Moderator:
Robin Toft, Author of WE CAN, The Executive Woman’s Guide to Career Advancement; Founder and Chairman, Toft Group Executive Search
Panelists: Camille Samuels, MBA, Partner, Venrock
Paul Hastings, President and CEO, Nkarta Therapeutics, Inc
Teresa L. Wright, MD, Staff Physician, Medicine, San Francisco Veterans Administration
8:00 Organizer’s Remarks
Christina Lingham, Executive Director, Conferences and Fellow, Cambridge Healthtech Institute
8:05 Chairperson’s Remarks
Stuart S. Martin, PhD, Professor, Physiology, Marlene and Stewart Greenebaum NCI Comprehensive Cancer Center, University of Maryland School of Medicine
8:10 FEATURED PRESENTATION: Cytophone Platform for in vivo Noninvasive Liquid Biopsy
Vladimir Zharov, PhD, DSc, Professor, Josephine T. McGill Chair in Cancer Research; Director, Arkansas Nanomedicine Center, Winthrop P. Rockefeller Cancer Institute, University of Arkansas for Medical Sciences; CSO, Cytoastra LLC
We developed the versatile Cytophone platform for real-time diagnosis and therapy (theranostics) of rare circulating disease markers in the whole blood pool (up to 5-liter) through intact skin. Based on the principle of photoacoustics, this platform
with portable and wearable sensors provides noninvasive (no blood draw, no needle), label-free (no label injection) and safe identification of a single marker of interest in relatively deep vessels in minutes. The broad spectrum of the Cytophone
application includes stroke prevention through circulating clot detection, diagnosis of infections (e.g., malaria), sickle anemia, and real-time drug efficiency monitoring, as well as diagnosis of other diseases by molecular targeting of CTCs
and other circulating markers with conjugated nanoparticles having high photoacoustic contrast.
8:40 Profiling Protein Expression for Individual CTCs
Shana O. Kelley, PhD, Professor, Department of Biochemistry, Leslie Dan Faculty of Pharmacy, University of Toronto
The analysis of heterogeneous ensembles of rare, circulating tumor cells (CTCs) requires single-cell resolution to allow phenotypic and genotypic information to be collected accurately. We developed a new approach – magnetic ranking cytometry
– that uses the magnetic loading of individual cells to be monitored as a means to report on biomarker expression at the single cell level. This approach can be used to profile circulating tumor cells in blood and provides a high-information
content liquid biopsy in a single measurement. It profiles both protein (Nature Nanotechnology, 2017) and nucleic acid (Nature Chemistry, 2018) analytes at the single-cell level. We have used this approach to monitor markers of the epithelial-to-mesenchymal
transition and predictors of response to therapy for lung and prostate cancer patient samples.
9:10 NEW: Tumor Antigen-Independent and Cell Size Variation-Inclusive Enrichment of Viable Circulating Tumor Cells via Integrated Ferrohydrodynamic Cell Separation (iFCS)
Leidong Mao, PhD, Professor, School of Electrical and Computer Engineering, University of Georgia
We developed a novel method based on contrast of cell magnetization in biocompatible ferrofluids, termed as integrated ferrohydrodynamic cell separation (iFCS), that enriches CTCs in a tumor antigen-independent and cell size variation-inclusive
manner, with a high-throughput, high recovery rate and low WBC contamination, and is also biocompatible.
Presentation delivered via a live, interactive video conferencing platform.
9:40 Refreshment Break in the Exhibit Hall with Poster Viewing, Speed Networking, Book Signing, and Meetup Group
Chairperson’s Remarks
Catherine Alix-Panabières, PhD, Director, Laboratory of Rare Human Circulating Cells (LCCRH), Pathology and Onco-Biology Department, University Medical Center of Montpellier
10:40 Novel Approaches to Large-Scale Collection and Downstream Analysis of Circulating Tumor Cells
Andrew Rhim, PhD, Associate Director for Translational Research, Ahmed Center for Pancreatic Cancer Research; Assistant Professor of Internal Medicine, UT MD Anderson Cancer Center
While current approaches to circulating tumor cells have focused on obtaining a relatively purified CTC population, such approaches hinder the study of larger numbers of cells and ex vivo expansion and characterization.
Here, we will discuss our strategies to enhance large-scale CTC collections, analysis of large numbers of CTCs, and in vitro expansion of CTCs.
11:10 Liquid Biopsy in Cancer Patients: A Focus on Metastasis-Initiator Circulating Tumor Cells
Catherine Alix-Panabières, PhD, Director, Laboratory of Rare Human Circulating Cells (LCCRH), Pathology and Onco-Biology Department, University Medical Center of Montpellier
Circulating tumor cells (CTCs) in blood are promising new biomarkers potentially useful for prognostic prediction and monitoring of therapies in patients with solid tumors, including colon cancer. Moreover, CTC research opens a new avenue for
understanding the biology of metastasis in cancer patients. However, an in-depth investigation of CTCs is hampered by the very low number of these cells, especially in the blood of colorectal cancer patients. Thus, the establishment of cell
cultures and permanent cell lines from CTCs has become the most challenging task over the past year. In this talk, we will discuss data that may supply insights for the discovery of new biomarkers to identify the most aggressive CTC sub-populations
and for the development of new drugs to inhibit metastasis-initiator CTCs in colon cancer.
11:40 Biology and Vulnerabilities of Circulating Tumor Cells (CTCs) and Multicellular CTC Clusters
Massimo Saini, PhD, Postdoctoral Researcher, Department of Biomedicine, University of Basel, Switzerland
Circulating tumor cells (CTCs) are itinerant cancer cells that transit through the bloodstream, where they mediate the hematogenous spread of cancer to distant organs. CTCs can travel as single, suspended cells or as multicellular CTC clusters.
Our lab has assessed the molecular phenotype and the metastatic potential of individual CTCs versus CTC clusters matched within individual blood samples, in breast cancer patients and in mouse models of CTC-mediated metastasis.
12:10 pm Analytical Validation of the RareCyte Platform for Circulating Tumor Cell Analysis in Global Clinical Trials
Jeff Fill, Senior Director, Diagnostic and Experimental Pathology, Lilly Research Laboratories, Eli Lilly and Company
Utilizing a risk-based approach, a novel platform for the enumeration of circulating tumor cells (CTC) was validated for clinical trial exploratory endpoint use and in partnership with a CRO was implemented in multiple global clinical trials.
12:40 Session Break
12:50 PRECISION HEALTH LUNCHEON PRESENTATION: Validation of A Next Generation Sequencing Gene Panel for Detection of Variants in Plasma Total Nucleic Acid
Xin-Xing Tan, PhD, Principal Scientist, Molecular, NeoGenomics Laboratories, Inc.
Liquid biopsy next generation sequencing (NGS) gene panel assays provide a powerful non-invasive tool to detect tumor-derived variants for clinic diagnostics in a massively parallel manner. We present here a NGS assay designed specifically for
liquid biopsy clinical applications, and its analytical and clinical validation to assess accuracy, specificity, sensitivity, repeatability, and reproducibility, etc.
1:20 Refreshment Break in the Exhibit Hall with Last Chance Poster Viewing, Speed Networking, Book Signing, and Meetup Group
2:00 Chairperson’s Remarks
Steven A. Soper, PhD, Professor, Micro and Nanofabricated Tools for Biological Discovery and Medical Diagnostics, University of Kansas
2:05 A Non-Invasive Liquid Biopsy Approach Using Urine-Derived Exosomes as a Biomarker Source for Predicting Treatment Outcomes in Cancer
Rajagopal Ramesh, PhD, Professor, Jim and Christy Everest Endowed Chair in Cancer Developmental Therapeutics, Oklahoma TSET Cancer Research Scholar, Department of Pathology; Director, Experimental Therapeutics and Translational Cancer Medicine;
Chair, Fellowship Training and Mentoring Program; Member, Stephenson Cancer Center, Stanton L. Young Biomedical Research Center
Exosomes are 30 - 120 nm cellular entities secreted from a variety of cell types and detectable in bodily fluids including urine. Studies demonstrate exosomes carry nucleic acids, proteins, lipids, etc., and can be used as source of biomarker.
In cancer, tumor-derived exosomes contribute to tumorigenesis, metastasis, and resistance to therapy. Based on these reports we undertook a non-invasive approach of isolating exosomes from urine samples collected from patients diagnosed with
non-small cell lung cancer (NSCLC) and receiving chemotherapy or chemotherapy plus anti-PD1 immunotherapy. We hypothesized that analysis of exosomal micro (mi) RNA and immune checkpoint proteins (ICP) will aid in predicting treatment outcomes.
To test our hypothesis urine samples were collected longitudinally before and after treatments from advanced NSCLC patients receiving chemotherapy or chemotherapy plus anti-PD1 immunotherapy. Exosomes were isolated by differential ultracentrifugation
method and analyzed for micro (mi) RNAs using the Illumina MiSeq platform and for immune checkpoint proteins (ICP) by ICP array. The results of the ongoing study will be discussed to demonstrate the feasibility of utilizing urine-derived exosomes
isolated from NSCLC patients as potential biomarker source for determining treatment outcomes.
2:35 Liquid Biopsies in Non-Oncological Diseases: Circulating Cells and Extracellular Vesicles as a Source of mRNA for the in vitro Diagnostics of Stroke
Steven A. Soper, PhD, Professor, Micro and Nanofabricated Tools for Biological Discovery and Medical Diagnostics, University of Kansas
Stroke is the third leading killer in the US and the main cause of over 795,000 cases of adult disability each year. The two major types of stroke, ischemic and hemorrhagic, cannot be clinically differentiated; 30% of patients presenting stroke-like
symptoms do not have stroke and <5% of stroke patients are treated with available therapeutics (recombinant tissue plasminogen activator for acute ischemic stroke). Computed tomography is commonly used for diagnosis, which provides a clinical
sensitivity of only 25%, and in most cases, does not provide clinical information to meet the necessary time requirements for proper therapeutic administration (<4.5 h). Unfortunately, there are no FDA-approved in vitro diagnostic tests for stroke that could address the aforementioned issues. In this presentation, we will provide data on the use of liquid biopsy markers, as well as isolation technologies and appropriate mRNA gene panels.
3:05 Close of Conference