Cambridge Healthtech Institute’s 7th Annual
Enabling Technologies for Liquid Biopsy and Beyond – Part 2
Developing Novel Assays for Circulating Biomarkers and Clinical Use
20-21 May 2020
Technologies for liquid biopsy are maturing and are continuing to improve sensitivity and specificity, and novel technologies for a number of biomarkers are being developed. These technologies, once developed, are branching out beyond typical cancer tests
to point-of-care assays or to fields, such as infectious disease. However, in order to broadly implement these assays, proper validation must be conducted. Cambridge Healthtech Institute’s Enabling Technologies for Liquid Biopsy and Beyond –
Part 2 will examine the latest advances in key technologies, novel biomarkers, and emerging clinical applications. We’ll examine analytical and pre-analytical challenges, the path to clinical use, and regulatory challenges.
Final Agenda
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WEDNESDAY 20 MAY
11:00 Registration
11:35 Breakout Discussions (Visit www.dxinnovationsummit.com/Breakout-Discussions for details)
TABLE: Exploring Multidimensional Liquid Biopsy Tests
Moderator: Vito Giuseppe D’Agostino, PhD, Group leader, Laboratory of Biotechnology and Nanomedicine, CIBIO, University of Trento, Italy
- Combination of multiple biological sources for liquid biopsy tests
- Create validated platforms making clinicians aware of novel breakthrough technologies
- Creation of networks for paralleling molecular analyses
TABLE: DNA Methylation-Based cfDNA Biomarkers
Moderator: Jason Ross, PhD, Principal Research Scientist, Health and Biosecurity, CSIRO, Australia
- The future of these biomarkers as liquid-biopsy tests for cancer
- What about outside of oncology?
- Bisulfite treatment, it’s the gold standard, but are the emerging alternatives useful for diagnostics?
12:35 Session Break
14:00 Keynote Introduction
Alain R. Thierry, PhD, Director of Research, Biomarkers for Precision Oncology, IRCM/INSERM, France
14:05 How Can a Network Enable Liquid Biopsy Introduction into the Clinic on a Large Scale?
Klaus Pantel, MD, Professor, Chairman, Institute of Tumor Biology, University Medical Center Hamburg-Eppendorf, Germany
The analysis of tumor cells (CTCs) and tumor cell products (DNA, miRNA, extracellular vesicles or tumor-educated platelets) in blood can provide clinically relevant information as “liquid biopsy”. To support the translation into clinical routine,
the European Liquid Biopsy Society was recently established based on the achievements of the EU/IMI sponsored consortium CANCER-ID (www.cancer-id.eu). Here, the opportunity of ELBS to transfer liquid biopsy research
into clinical practice will be outlined and discussed.
14:35 Donor-Derived Cell-Free DNA Testing in Organ Transplantation: A Value Proposition
Michael Oellerich, MD, Hon MD, FAACC, FAMM, FFPath (RCPI), FRCPath, Distinguished Research Professor, Clinical Pharmacology, University Medical
Center Goettingen (UMG), Germany
There is a need to improve personalized immunosuppression in organ transplantation to reduce premature graft loss. A value proposition concept was applied for donor-derived cell-free DNA testing in plasma of transplant recipients as an alternative to
invasive biopsies to early detect or exclude rejections or other graft injuries. This approach allows to personalize immunosuppression and may improve outcome. Transplant physicians could provide better immunosuppressive guidance. Hospital management
and insurance companies benefit from more cost-effective surveillance of transplant recipients.
15:05 Detection of Cell-Free Circulating BRAFV600E by Droplet Digital PCR in Patients with Melanocytic Cutaneous Lesions: Considerations for the Clinical Implementation
Joan Anton Puig-Butille, PhD, Head, Molecular Biology CORE, Hospital Clinic of Barcelona, Spain
The p.V600E mutation in BRAF gene (BRAFV600E) is frequently detected in melanoma and common benign naevi. We evaluated the clinical significance of detection of BRAFV600E in plasma cfDNA (cfBRAFV600E) from melanoma patients and from patients without melanoma
undergoing regular follow-up of their melanocytic lesions. The study suggests that naevus-related factors do not influence the detection of cfBRAFV600E and supports the clinical diagnostic value of cfBRAFV600E quantification in melanoma patients.
15:35 Presentation to be Announced
16:05 Refreshment Break in the Exhibit Hall with Poster Viewing
17:00 Chairperson’s Remarks
Daniel Wetterskog, PhD, Senior Research Associate, UCL Cancer Institute, University College London, United Kingdom
17:05 Sample to Answer Multi-Omic Exosome and cf-DNA Biomarker Detection for Liquid Biopsy Diagnostics
Michael Heller, PhD, Professor and Distinguished Scientist, Center for Cancer Early Detection and Research (CEDAR), Knight Cancer Institute, Oregon
Health & Science University (OHSU), United States
New multi-omic approaches for combining genomic and proteomic biomarker information are becoming a viable strategy for liquid biopsy diagnostics. Electrokinetic samples to answer ACE microarray chip devices now allow rapid isolation of exosomes/EV biomarkers,
cell free (cf) DNA and RNA from small volumes of cancer patient blood samples. On-chip fluorescent detection of cf-DNA levels, immunostaining for specific exosome/EV protein biomarkers and subsequent sequencing analysis for point mutation biomarkers
were successfully carried out on blinded patient samples for pancreatic cancer diagnostics.
17:35 Clinical Application of Ultrasensitive Sequencing of Cell-Free Tumor DNA and Immune Cells
Anders Ståhlberg, Associate Professor, Sahlgrenska Cancer Center, University of Gothenburg; Clinical Genetics & Genomics, Sahlgrenska University
Hospital, Sweden
Detailed analysis of cell-free tumor DNA and immune-cell clonality in liquid biopsies requires ultrasensitive sequencing. We have developed simple, flexible and sensitive approaches to analyze DNA from various cell sources, as well as from circulating
cell-free DNA. Here, we will present our experiences of using ultrasensitive analysis from both a clinical and technical point of view. Data from different applications will be shown.
18:05 A Multi-Omic Strategy for Cancer Diagnostics and Monitoring
Michael Roehrl, MD, PhD, Associate Professor of Pathology and Laboratory Medicine, Pathology and Human Oncology and Pathogenesis Program, Memorial Sloan
Kettering Cancer Center, United States
An integrated approach to cancer that encompasses combining genomics, transcriptomics, and epigenomics with deep proteomics promises to become a powerful tool for cancer diagnosis, personalized treatment guidance, resistance detection, and recurrence
monitoring. We will discuss several examples using such combined approaches (including gastrointestinal cancers and sarcomas), new technological and specimen-directed advances for correlating circulating and tissue-resident cancer markers, and the
computational challenges that arise from multi-omic big data analytics.
18:35 Close of Day
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THURSDAY 21 MAY
08:30 Registration and Morning Coffee
09:00 Chairperson’s Remarks
Catherine Alix-Panabieres, PhD, Director, Laboratory of Rare Human Cells (LCCRH), Department of Pathology and Onco-Biology, University Medical Centre of Montpellier, France
09:05 Detection, Characterization and ex vivo Expansion of Viable Circulating Tumor Cells (CTCs)
Catherine Alix-Panabieres, PhD, Director, Laboratory of Rare Human Cells (LCCRH), Department of Pathology and Onco-Biology, University Medical
Centre of Montpellier, France
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. The establishment of cell cultures and permanent cell lines from CTCs has become the most challenging task over the past year.
09:25 Capture of Circulating Tumour Cell Clusters Using Straight Microfluidic Chips
Chamindie Punyadeera, PhD, Associate Professor, Biomedical Sciences, Queensland University of Technology, Australia
We have demonstrated that CTCs can be isolated from head and neck cancer (HNC) patients before clinically evident metastasis, using a novel, spiral microfluidic technology and now we have exciting preliminary data correlating CTC presence to clinical
outcomes during the course of treatment. Using the state of the art technology, straight channel microfluidic technology, we have been able to detect CTC clusters from HNC, non-small cell lung cancer and glioblastoma. These clusters contain two or
more CTCs and leukocytes and were found in advanced stage cancer patients. This microfluidic technology has the ability to transform scientific findings into translational outcomes and tangible health benefits with a significant reduction in healthcare
costs.
09:45 Patient-Derived Circulating Tumor Cells as a Predictor of Treatment Response and Survival
Prashant Kumar, PhD, Faculty Scientist, Cancer Biology, Institute of Bioinformatics, India
Monitoring CTCs is a valuable strategy for guiding patient treatment, predicting cancer progression, and evaluating the risk for metastatic relapse. We have devised a microwell-based culture method to assess CTCs from patients undergoing neoadjuvant therapy.
The culture method allowed selective enrichment of CTCs that went on to form proliferative clusters. Cluster formation was affected by the presence and duration of systemic therapy and its persistence may reflect therapeutic resistance.
10:05 Sponsored Presentation (Opportunity Available)
10:35 Coffee Break in the Exhibit Hall. Last Chance for Poster Viewing
11:20 Mutational Analysis of Circulating Tumor Cells at the Single-Cell Level
Pamela Pinzani, PhD, Associate Professor, Clinical, Experimental and Biomedical Sciences, University of Florence, Italy
11:50 CO-PRESENTATION: Molecular Tagging NGS Technology in Liquid Biopsy: Mutational Profiling of ctDNA and CTCs
Maria Dono, PhD, Senior Researcher, Pathology, Molecular Diagnostics, IRCCS Ospedale Policlinico San Martino, Italy
Giuseppa De Luca, PhD, Postdoc Research Fellow, Pathology, Molecular Diagnostic, IRCCS Ospedale Policlinico San Martino, Italy
Molecular analysis of liquid biopsy biomarkers, resembled primarily by circulating tumor DNA and cells (CTCs) is technically challenging. The development of NGS panels, molecular tagging-based, gives a relevant chance for their accurate molecular characterization.
Here, we will discuss some data developed by using commercial NGS assays for the study of ctDNA in NSCLC patients and CTCs isolated from breast cancer patients.
12:20 Sponsored Presentation (Opportunity Available)
12:50 Luncheon Presentation (Sponsorship Opportunity Available) or Enjoy Lunch on Your Own
13:20 Session Break
13:50 Chairperson’s Remarks
Christa Noehammer, PhD, Senior Scientist, Molecular Diagnostics, AIT Austrian Institute of Technology GmbH, Austria
14:00 An Exosome-Based Liquid Biopsy for Detection of Melanoma Residual Disease
Susana García-Silva, PhD, Senior Researcher, Oncology Program, Spanish National Cancer Research Centre (CNIO), Spain
Tumor-derived extracellular vesicles carry a portrait of the cancer cells and associated microenvironment. Our data show that extracellular vesicles isolated from the lymphatic exudate of melanoma patients can be interrogated for melanoma markers and
BRAF mutations. Profiling the BRAFV600 mutation in lymph-circulating EVs is a novel prognostic approach to predict residual disease after tumor resection and lymphadenectomy.
14:30 A Liquid Biopsy PCR Assay to Detect Cell-Free DNA from Dying Neurons and Glia
Jason Ross, PhD, Principal Research Scientist, Health and Biosecurity, CSIRO, Australia
In head trauma, DNA from dying brain cells is released into peripheral blood. Using the DNA methylation marks present on this brain cell-free DNA (cfDNA), it is possible to discretely identify brain cfDNA against the usual blood background. Applying this
principle, we have developed a PCR diagnostic assay which can specifically detect small quantities of cfDNA from dying neurons and glia. Recently, we have commenced clinical trials.
15:00 Rapid Nickel-Based Isolation of Extracellular Vesicles for Multidimensional Liquid Biopsy Tests
Vito Giuseppe D’Agostino, PhD, Group Leader, Laboratory of Biotechnology and Nanomedicine, CIBIO, University of Trento, Italy
Extracellular vesicles (EVs) are membranous structures massively released in biofluids. EVs carry cellular components, such as lipids, proteins, and nucleic acids, that can work as a formidable source in liquid biopsy studies. We recently described
the nickel-based isolation (NBI) as a versatile method for fast and efficient recovery of heterogeneous EVs. We combined NBI with RNA- , as well as protein-based ultrasensitive technologies, improving the detection of biomarkers under clinical
use.
15:30 Pan-Genome cfDNA Methylation Analysis of Metastatic Prostate Cancer
Anjui Wu, PhD, MD, Postdoctoral Research Fellow, UCL Cancer Institute, University College London, United Kingdom
Genomic profiling of cfDNA has been well described in multiple tumour types, including lung cancer, colon cancer and prostate cancer; however, the cfDNA methylation status has not been extensively studied. I will present our unpublished work on cfDNA
methylation analysis of metastatic prostate cancer, and our data indicated that plasma methylome has great potentials for cancer screening, detection and risk stratification.
16:00 Close of Conference
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