Cambridge Healthtech ’s 4th Annual
Enabling Technologies for Circulating Biomarkers
Advancing Technologies for Clinical Utilities
August 20-21, 2019
The technologies in the liquid biopsy field have been maturing rapidly and are on their path to revolutionize the management of cancer patients. However, in the increasingly crowded landscape of all the diagnostic approaches, it can be overwhelming to
identify the key technologies that are showing promises and have
potential to be implemented in clinical practices. Cambridge Healthtech Institute’s Fourth Annual Enabling Technologies for Circulating Biomarkers conference will bring together experts in the field to validate and uncover promising emerging
technologies for liquid biopsy applications that make use of diverse biomarker types such as CTCs, cfDNA, RNA, exosomes
and platelets. In addition, we will also emphasize the discussions around the harmonization and standardization of all the testing procedures from pre-analytical, analytical, to post-analytical phases of a diagnostic test process.
Final Agenda
Recommended Short Course*
SC3: Emerging Applications of ctDNA
John Simmons,
PhD, Vice President, Translational Medicine, Personal Genome Diagnostics
This short course will cover cutting edge applications and clinical trials that use ctDNA for monitoring, minimal residual disease, and plasma tumor mutation burden. The background basics, the technologies, the clinical evidence out there so far, and
the highlights of the prospective designs that are underway will be discussed.
Franklin/McPherson
SC9: Liquid Biopsies based on Extracellular Vesicles: Prospects, Challenges, and Opportunities
Joshua T. Smith,
PhD, Research Staff Member and Silicon Development Team Leader, Translational Systems Biology and Nanobiotechnology, IBM T. J. Watson Research Center
Extracellular vesicles (EVs) exhibit a number of properties that make them attractive as a rich source of biomarkers for disease diagnosis, treatment monitoring, and therapeutics, including their abundance in a wide breadth of bodily fluids, nucleic acid
and protein content, and protective lipid membrane that preserves this cargo from degradation. This course reviews key discoveries in EV research, describes current efforts to exploit their properties to capture market value, and takes a look
at exploratory and emerging technologies aimed at accelerating their study and use. Existing gaps in understanding along with current efforts to address these unknowns will also be elucidated.
Cabin John
*Separate registration required.
TUESDAY, AUGUST 20
7:30 am Registration and Morning Coffee
8:30 Chairperson’s Opening Remarks
Sam Hanash, MD,
PhD, Director, Red & Charline McCombs Institute; Evelyn & Sol Rubenstein Distinguished Chair, Cancer Prevention; Professor, Clinical Cancer Prevention-Research, Translational Molecular Pathology, University of Texas MD Anderson Cancer
Center
8:40 KEYNOTE PRESENTATION: Precision Medicine Using Liquid Biopsies: A New Paradigm for Managing Cancer Diseases
Steven A. Soper, PhD,
Chemistry, Mechanical Engineering, BioEngineering, KUMC Cancer Center University of Kansas, Lawrence; Director, NIH Biotechnology Resource Center of BioModular Multi-Scale Systems for Precision Medicine
We are generating innovative microfluidic tools for selecting circulating markers from whole blood and determining the presence/absence of disease-specific molecular signatures secured from the liquid biopsy markers to guide therapy for a patient. The
microfluidics can process whole blood (≥1 mL) and search for CTCs, cfDNA, or exosomes and make them available for downstream molecular processing. I will talk extensively about our exosome isolation chip, and its use in several clinical examples
and securing molecular information from the affinity-selected exosomes. The exosome chip consists of 1.4 million pillars that contain surface-immobilized antibodies directed against antigens from cancer cells that are
epithelial based (EpCAM) and those with a mesenchymal phenotype (
fibrobast activation protein alpha, FAPα). The chip is operated by a robotic workstation and can perform 32 isolation assays per day per machine in a fully automated fashion.
9:10 Opportunities and Challenges for Liquid Biopsies in the Fight Against Cancer
Lynn R. Sorbara, PhD, Program Director, Cancer Biomarker Research Group, National Cancer Institute
This presentation will address the need for better focus on the clinical decision making support being enabled by liquid biopsy-based assays in the context of new enabling technologies that are shaping the landscape of possibilities. The persistent need
for standards development in this field to qualify new assays are
a critical components for that, and as promising as ctDNA is we know we can’t throw out consideration of CTCs.
9:40 Multi-Parametric Liquid Biopsy Analysis in Metastatic Prostate Cancer
Amir Goldkorn, MD,
Associate Professor of Medicine, Co-Leader, Translational & Clinical Science Program; Director, Circulating Tumor Cell Research Core, USC Norris Comprehensive Cancer Center & Keck School of Medicine; Chair, Prostate Cancer Organ Site Translational
Medicine, SWOG
Multiparametric liquid biopsy profiles were successfully generated for each patient and time point, demonstrating the feasibility of this approach and highlighting shared as well as unique cancer-relevant alterations. With further refinement and validation
in large cohorts, multiparametric liquid biopsies can optimally integrate disparate but clinically informative data sets and maximize their utility for molecularly directed, real-time patient management.
10:10 Coffee Break in the Exhibit Hall with Poster Viewing
10:55 Chairperson’s Remarks
Sam Hanash, MD,
PhD, Director, Red & Charline McCombs Institute; Evelyn & Sol Rubenstein Distinguished Chair, Cancer Prevention; Professor, Clinical Cancer Prevention-Research, Translational Molecular Pathology, University of Texas MD Anderson Cancer
Center
11:00 Multi-Omic Liquid Biopsy Platform
Sam Hanash, MD,
PhD, Director, Red & Charline McCombs Institute; Evelyn & Sol Rubenstein Distinguished Chair, Cancer Prevention; Professor, Clinical Cancer Prevention-Research, Translational Molecular Pathology, University of Texas MD Anderson Cancer
Center
Multiple technologies are currently being explored for liquid biopsy applications beyond genomics, including proteomics, metabolomics,
immunomics
and extra-cellular vesicles. The individual and combined contributions of these approaches will be presented.
11:30 Analysis of Therapeutically-Relevant Markers in Circulating Tumor Cells
Shana O. Kelley,
PhD, Professor, Leslie Dan Faculty of Pharmacy, Faculty of Medicine, Biochemistry, University of Toronto
12:00 pm An Open Platform for CTC Analysis: Identification, Phenotypic Characterization and Molecular Analysis
Arturo Ramirez, Director, Oncology R&D, RareCyte, Inc.
This talk will highlight the unique benefits of the RareCyte platform for CTC characterization. It will present the method to transfer nucleated cells from whole blood to slides as well as immunofluorescence staining to identify CTCs and phenotypically
characterize clinically relevant biomarkers. Clinical studies were performed comparing our platform to CellSearch® and single CTCs were isolated for next generation sequencing to obtain molecular information about the tumor via liquid biopsy.
12:30 Luncheon Presentation (Sponsorship Opportunity Available) or Enjoy Lunch on Your Own
1:00 Cookie & Refreshment Break in the Exhibit Hall with Poster Viewing
1:30 Chairperson’s Remarks
Steven A. Soper,
PhD, Chemistry, Mechanical Engineering, BioEngineering, KUMC Cancer Center University of Kansas, Lawrence; Director, NIH Biotechnology Resource Center of BioModular Multi-Scale Systems for Precision Medicine
1:35 Targeting CTC Cytoskeletal Alterations to Reduce Metastasis
Stuart Martin,
PhD, Professor, Greenebaum Comprehensive Cancer Center, University of Maryland School of Medicine
2:05 Isolation of Circulating Tumor Cells in Non-Small-Cell-Lung-Cancer Patients Using a Multi-Flow Microfluidic Channel
Ian Papautsky,
PhD, Professor, Bioengineering; Co-Director, NSF Center for Advanced Design & Manufacturing of Integrated Microfluidics (CADMIM) Bioengineering,
University of Illinois at Chicago
Our device is constructed and configured based on the phenomenal effect of size-dependent inertial migration. The recovery rate of >93%
has been achieved using spiked cancer cells at clinically relevant concentrations (10 cells per 5 mL and above). We have also successfully detected CTCs from 6 out of 8 non-small-cell-lung-cancer (NSCLC) patients, while none for 5 healthy
control subjects. With these results, we envision our approach is a promising alternative for reliable CTC capture, and thus for facilitating the progress of extracting information from CTCs to personalize treatment strategies for solid tumor
patients.
2:35 Detection and Analysis of Circulating Epithelial Cells in Liquid Biopsies from Patients with Liver Disease
Irun Bhan, MD, Clinical Instructor, Harvard Medical School, Transplant Hepatologist, Division of Gastroenterology, Massachusetts General Hospital
In this work, we used the iChip platform to detect CECs in patients with CLD but without HCC and to phenotypically discriminate between CECs in patients with and without HCC.
3:05 Attend Concurrent Tracks
3:35 Refreshment Break in the Exhibit Hall with Poster Viewing
4:25 Chairperson’s Remarks
G. Mike Makrigiorgos,
PhD, Professor of Radiation Oncology, Dana Farber Cancer Institute and Harvard Medical School
4:30 Novel Digital PCR and Mutation Enrichment Technologies for the Analysis of Clinically Relevant DNA Alterations in Liquid Biopsies
G. Mike Makrigiorgos,
PhD, Professor of Radiation Oncology, Dana Farber Cancer Institute and Harvard Medical School
With the increasing interest in treatment assessment using liquid biopsy and circulating DNA, sensitive and multiplexed detection of tumor-derived alterations in blood are desirable. We provide novel forms of digital PCR, as well as mutation enrichment-based
real time PCR methods that (a) enable several orders of magnitude improvement of detecting mutations or microsatellite instability than currently possible; (b) are highly multiplex-able; (c) reduce
cost of analysis. Application in circulating DNA from clinical cancer samples will be presented.
5:00 Phospho-sRNA-seq Enables Plasma mRNA/lncRNA Transcriptome Profiling as a Liquid Biopsy Approach
Ryan M. Spengler,
PhD, Postdoctoral Fellow, Muneesh Tewari Laboratory, Hematology/Oncology, University of Michigan
We present a modified RNA-seq methodology, called
phospho-sRNA-seq, which, when combined with a stringent computational pipeline, allows enhanced profiling of extracellular mRNA and lncRNAs in blood plasma. We find that
signal comes from transcript fragments that are detected across individuals, and demonstrate dynamic expression patterns consistent with physiological changes in patients. Together, our methods increase access to extracellular transcriptome
signatures, providing additional avenues to uncover RNA biomarkers in liquid biopsies.
5:30 Digital Counting of Target cfRNA and cfDNA with NanoString nCounter® Technology
Adam Abdool, Senior Product Manager, Life Sciences, NanoString
Liquid (versus tissue) biopsy offers advantages for early disease diagnosis, progression monitoring and evaluation of therapeutic interventions because sample collection is rapid, easy, minimally invasive, and repeatable. However, detection
has been difficult due to low abundance of target molecules, leading to complex workflows with highly variable signal detection. We’ll demonstrate utilizing nCounter technology for liquid biopsy applications (Research Use Only), including
mutation detection of ctDNA & RNA profiling, and fusion detection of cfRNA.
6:00 Wine & Cheese Pairing Welcome Reception in the Exhibit Hall with Poster Viewing
7:00 Close of Day
WEDNESDAY, AUGUST 21
7:15 am Registration
Independence B-E and Foyer
7:30 Problem Solving Breakout Discussions with Continental Breakfast
Analytical Considerations for Liquid Biopsy RNA-seq
Moderator: Ryan M. Spengler, PhD, Postdoctoral Fellow, Muneesh Tewari Laboratory, Hematology/Oncology, University of Michigan
- Quality control measures and sample assessment
- Mapping and quantification: dealing with contaminates and ambiguous alignments
- Pitfalls of expression analysis: sequencing bias, normalization and differential expression
Challenges for Early Cancer Detection
Moderator: Michael J. Heller, PhD, Distinguished Scientist, Knight Cancer Institute at Oregon Health & Science University (OHSU), Center for Cancer Early Detection and Research (CEDAR); Professor Emeritus, Bioengineering and Nanoengineering,
University of California San Diego
- Which biomarkers?
- Problem of extremely low biomarker levels in blood
- Viable technology to meet these challenges
8:25 Chairperson’s Remarks
Hyungsoon Im,
PhD, Assistant Professor of Radiology, Massachusetts General Hospital, Radiology, Massachusetts General Hospital
8:30 Ultrasensitive Detection of Circulating Exosomes with a 3D-Nanopatterned Microfluidic Chip
Yong Zeng,
PhD, Associate Professor and Docking Faculty Scholar, Chemistry, KU Cancer Center, University of Kansas
Here, we show that a microfluidic chip designed with self-assembled three-dimensional herringbone nanopatterns can detect low levels of
tumour-associated exosomes in plasma (10 exosomes μl−1, or approximately 200 vesicles per 20 μl of
spiked sample) that would otherwise be undetectable by standard microfluidic systems for biosensing. The nanopatterns promote microscale mass transfer, increase surface area and probe density to enhance the efficiency and speed of
exosome binding, and permit drainage of the boundary fluid to reduce near-surface hydrodynamic resistance, thus promoting particle–surface interactions for exosome binding.
9:00 AC Electrokinetic Chip Device for Rapid Isolation and Integrated Analysis of Exosome and cf-DNA Biomarkers from Cancer Patient Blood Samples
Michael
J. Heller,
PhD, Distinguished Scientist, Knight Cancer Institute at Oregon Health & Science University (OHSU), Center for Cancer Early Detection and Research (CEDAR); Professor Emeritus, Bioengineering
and Nanoengineering, University of California San Diego
New multi-omic approaches for different biomarkers is becoming a viable strategy for liquid biopsy diagnostics and early cancer detection.
Electrokinetic sample to answer ACE chip devices were used for the rapid isolation of exosomes, extracellular vesicles (EVs) and
cell free (cf) DNA/RNA from cancer patient plasma samples. Subsequent fluorescent detection of cf-DNA levels, immunostaining for specific exosome/EV protein biomarkers and ddPCR/sequencing analysis for point mutations were all carried
out.
9:30 Nanoplasmonic Exosome (
nPLEX) Technology for Circulating Tumor Exosome Profiling
Hyungsoon
Im,
PhD, Assistant Professor of Radiology, Massachusetts General Hospital, Radiology, Massachusetts General Hospital
Exosomes have emerged as promising circulating biomarkers for diagnosis and prognosis of various cancer types. This presentation will discuss
a recent progress of
nPLEX (nano-plasmonic exosome) technology that we developed for sensitive detection and molecular profiling of circulating exosomes for ovarian and pancreatic cancers.
10:00 High Precision Isolation and Analysis of Exosomes
Daniel T. Chiu, PhD, A. Bruce Montgomery Professor, Chemistry and Bioengineering, University of Washington, Seattle
We have recently developed microfluidic and nanofluidic systems for the isolation and analysis of exosomes, offering detailed molecular information with single-exosome resolution. Here, we will describe our technical approach, device performance,
and the new information we learned about exosomes as revealed by the new measurements.
10:30 Coffee Break in the Exhibit Hall with Poster Viewing
Constitution A&B
11:30 Plenary Keynote Session
11:30 Chairperson’s Remarks
Charles Mathews, Principal, ClearView Healthcare Partners
11:40 NEW: Plenary Keynote Presentation: FDA Updates: Now and Looking to the Future
Katherine Donigan, PhD, Acting Director of Personalized Medicine, Office of In Vitro Diagnostics and Radiological Health, Center for Devices and Radiological Health, U.S. Food and Drug Administration
Introduction and background of the new Office Director of OIR and updates on precision medicine and other initiatives at the FDA.
12:10-1:05 pm Plenary Keynote Discussion: Proposals and Solutions for Diagnostic Reform Including Oversight of Laboratory Developed Tests (LDTs)
Moderator:
Cynthia A. Bens, Senior Vice President, Public Policy, Personalized Medicine Coalition
- How are stakeholders influencing congressional activity on the Verifying Accurate Leading-edge IVCT Development (VALID) Act?
- How will the VALID Act change the current oversight landscape for diagnostics, including LDTs?
- How are policymakers addressing the role of CMS and CLIA in the VALID Act?
- How will increased regulatory and oversight activities at the FDA affect the diagnostics industry?
- What impact will changes in diagnostics regulation and oversight have on patient care?
Panelists:
Julie Khani, MPA, President, American Clinical Laboratory Association (ACLA)
Donald E. Horton, Jr., Senior Vice President, Global Government Relations & Public Policy, Laboratory Corporation of America Holdings
Susan Van Meter, Executive Director, AdvaMedDx
Tara Burke, PhD,
Senior Director, Public Policy & Advocacy, Association for Molecular Pathology (AMP)
Laura Lasiter, PhD, Science Policy Analyst, Friends of Cancer Research
1:05 pm Luncheon Presentation (Sponsorship Opportunity Available) or Enjoy Lunch on Your Own
1:35 End of Enabling Technologies for Circulating Biomarkers