Cambridge Healthtech Institute’s 7th Annual

Enabling Technologies for Liquid Biopsy and Beyond - Part 1

Developing Novel Assays for Circulating Biomarkers and Clinical Use

19-21 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 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

MONDAY 18 MAY

Recommended Short Course*

SC2: Biomarkers in Liquid Biopsy: CTCs, ctDNA and Exosomes - Detailed Agenda

*Separate Registration required.

TUESDAY 19 MAY

THE IMPORTANCE OF BIG DATA IN LIQUID BIOPSY

08:00 Registration and Morning Coffee

08:55 Organizer’s Opening Remarks

Kaitlin Searfoss Kelleher, Senior Conference Director, Cambridge Healthtech Institute

09:00 Chairperson’s Remarks

Michael Oellerich, MD, Hon MD, FAACC, FAMM, FFPath (RCPI), FRCPath, Distinguished Research Professor, Clinical Pharmacology, University Medical Center Goettingen (UMG), Germany

 

 

09:05 The First WHO International Standards for Circulating Tumour DNA: Towards Global Harmonisation of Liquid Biopsy Measurement

Angela Pia Sanzone, PhD, Blood Biomarkers Group Leader, Advanced Therapies Division, National Institute for Biological Standards and Control (NIBSC), Italy

The adoption of ctDNA measurement into routine clinical practice would be strengthened by the availability of internationally recognized reference standards, enabling harmonised reporting in diagnostics and patient monitoring. NIBSC (UK) is developing WHO International Standards for ctDNA, initially for EGFR variants, intended to be maximally commutable, and complementing in parallel-developed genomic DNA standards for direct solid tumour diagnostics, thus facilitating accurate, consistent measurement of cancer biomarkers in liquid biopsy.

UPDATES IN LIQUID BIOPSY TECHNOLOGIES

9:35 Fragmentomics as Novel Strategy to Characterize Circulating DNA: Application to Cancer Screening

Alain Thierry, PhD, Director of Research, Biomarkers for Precision Oncology, IRCM/INSERM, France

Most of nuclear circulating DNA (cirDNA) is highly fragmented upon chromatin organization and protection/packaging within mononucleosomes, as the lowest unit and the most stabilized structure in the blood stream. Size pattern characterization or fragmentomics is related to the nucleosomal packing of DNA and the interaction with histone proteins. Fragmentomics may determine tissue-of-origin, and as well classify fetal and cancer derived cirDNA vs healthy individuals. This confirmed our earlier hypothesis that fragmentomics is a strategy to characterize cancer individuals appearing as an alternative or a synergistic supplement to searching mutations, methylation or nucleosome positioning to further improve diagnostics and cancer screening.

10:05 Presentation to be Announced

 

10:20 Sponsored Presentation (Opportunity Available)

10:35 Grand Opening Coffee Break in the Exhibit Hall with Poster Viewing

UPDATES IN LIQUID BIOPSY TECHNOLOGIES

11:15 Enabling Technologies for Low-Cost and Efficient Targeted Re-Sequencing for Liquid Biopsy Applications

Makrigiorgos_MikeG. Mike Makrigiorgos, PhD, Professor, Radiation Oncology, Dana-Farber Cancer Institute and Harvard Medical School, United States

As the potential of liquid biopsies for prognostic, predictive or early cancer detection applications grows, so does the demand for technical advances to accompany the burgeoning range of applications. We present new developments that enable targeted re-sequencing for liquid biopsy applications at a fraction of the current cost, while retaining or increasing sensitivity and specificity. Examples for detecting low-level mutations in circulating DNA will be presented.

11:45 Detection of Point Mutations in Liquid and Tissue Biopsy Using an Acoustic Wave Array Platform

Nikoletta Naoumi, MSc, PhD Student, IMBB-FORTH, Greece

The project concerns the development of a novel ultra-sensitive diagnostic method for the detection of single-copy point mutations in circulating and genomic tumor DNA for liquid and tissue biopsy, respectively. The approach involves the use of a highly sensitive and specific allele-specific PCR assay combined for the first time with an acoustic biosensor. The work is part of the CATCH-U-DNA EU-funded Horizon2020 FET-OPEN project.

12:15 New Markers to Highlight Circulating Tumor DNA for Colon Cancer Patient Follow-Up

Geoffrey Poulet, PhD Student, Valerie Taly's Lab, Translational Research and Microfluidics, Eurofins-BIOMNIS, France

Recent technological developments including droplet-based digital PCR and optimized NGS have greatly facilitated the tracking of circulating cell-free nucleic acids in body effluents. Strategies dedicated to the detection of circulating tumor DNA based on multiple innovative markers, such as DNA hypermethylation or DNA integrity, will be presented. In particular, we will illustrate the pertinence of these approaches for the follow-up of patients with localized or advanced colorectal cancers.

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12:45 Nu.QTM Complete – Comprehensive Nucleosome Profiling

Mark Eccleston, PhD, MBA, Director, Business Development, Volition, Belgium

Volition is utilising epigenetic profiling of cell-free, circulating nucleosomes using simple Nu.Q immunoassays to develop blood tests for early detection of a range of cancers. We now present a broader analytical approach, employing immuno-capture, mass spectrometry, immunoassay and sequencing of constituent DNA to allow comprehensive analysis of circulating nucleosomes of tumor origin.x

13:15 LUNCHEON PRESENTATION: Advances in CTCIsolation and Characterisation Using the Epitope-Independent Parsortix System

Anne-Sophie Pailhes-Jimenez, R&D Group Leader, Cell Biology and Imaging – R&D, ANGLE plc, United Kingdom

Circulating tumor cells (CTCs) can provide access to protein and genetic information on patient cancer through a simple blood draw. The enumeration of CTCs has shown prognostic relevance in several cancer types. The Parsortix system allows epitope-independent capture and harvest of CTCs from blood for analysis. We developed a robust workflow allowing for epithelial and mesenchymal CTC identification and characterisation from cancer patient samples using immunofluorescence. The presented workflow would provide a complete and standardised sample-to-answer imaging solution, from blood separation to images of CTCs.

13:45 Session Break

LIQUID BIOPSY FOR INFECTIOUS DISEASE

14:15 Chairperson’s Remarks

Clare Morris, BSc, Principal Scientist, Division of Infectious Disease Diagnostics, National Institute for Biological Standards and Control, United Kingdom

14:20 FEATURED PRESENTATION: A Universal Cancer Assay With Applications in Infectious Disease: Are We There Yet?

Trau_MattMatt Trau, PhD, Deputy Director and Co-Founder, Australian Institute for Bioengineering and Nanotechnology; Professor, Chemistry, University of Queensland, Australia

The Centre for Personalised Nanomedicine at UQ is focused on translating nanotechnologies into a clinical setting, whilst developing the next generation of point-of-care diagnostic technologies to further empower the personalised and precision medicine approach. Our consortium recently published hundreds of epigenetic regions that are highly informative in cancer, as well as a unique epigenetic marker that appears to be universal for cancer. In this talk we will present data on the clinical translation of this approach, highlighting some of the positive impacts that such an approach can make. Along with comprehensive DNA/RNA/methylated-DNA sequencing methodologies, several point-of-care nanotechnologies recently developed by our lab will be presented.

14:45 Liquid Biopsy for Neuroinvasive Arbovirus Diseases

François Jean, PhD, Associate Professor, Microbiology and Immunology, University of British Columbia; Team Leader, NSERC CRD Grant in 3-D Brain Organoid Models of Arboviral Diseases; Co-Founder, Canadian Network of Scientific Platforms, Canada

Arboviruses (arthropod-borne viruses), such as Zika virus (ZIKV), are responsible for a significant health burden worldwide. ZIKV is now the second-most widely distributed arbovirus in the Americas. ZIKV infections produce different neurologic complications in different individuals which are difficult to diagnose virologically. Dr. Jean will present the development of “liquid biopsy” for ZIKV-associated neurological diseases. With the recent discovery of circulating extracellular vesicles (EVs) and their important cellular functions in arboviral infections and diseases, Dr. Jean’s team hypothesizes that brain-derived (BD) EVs released during viral infection represent unexplored treasure troves of potential host-biomarkers for neuroinvasive arboviral diseases. For proof-of-concept, Dr. Jean will report the molecular and biophysical characterization of BD EVs released from ZIKV-infected human cerebral organoids and discuss the impact of their findings for developing next-generation molecular diagnostics technology for neuroinvasive arbovirus infection.

15:10 How Good Is Your Assay and Can You Prove It?

Clare Morris, BSc, Principal Scientist, Division of Infectious Disease Diagnostics, National Institute for Biological Standards and Control, United Kingdom

Consistent and effective clinical management of diseases requires comparable data generated by diagnostic assays. With each advancement of technology, we see new challenges, especially in the field of molecular assays. Whilst many laboratories acknowledge the need for validated assays and calibrated controls, there is great variation in methods to determine assay accuracy. Thus, even though a standard may exist, it serves little function if not used correctly. This presentation will address the application of these types of reference materials linked to a primary physical reference. “The International Standard”, wherever possible, can provide assurance of the quality of the data and, in turn, support improved clinical management of patients.

15:30 Development of Proteomic Signatures for Use in Precision Medicine

Anthony Whetton, PhD, Director, Stoller Biomarker Discovery Centre, University of Manchester, United Kingdom

Precision medicine is a key objective in improving healthcare. The use of innovations in MS-based technologies offers high-capacity throughput proteomic profiling for clinical biochemistry purposes, as has been achieved at the Stoller Biomarker Discovery Centre. For example, markers of risk in ovarian cancer and response to therapy in schizophrenia have been investigated using a Data Independent Acquisition (DIA) mass spectrometry approach, among other uses. Combined with validation platforms, this approach offers a quicker route to mechanistic detail/drug targets, plus biomarkers for risk and stratification. New approaches to biomarker discovery are also coming to the fore using artificial intelligence approaches.

15:50 Lyophilization Solutions for Assay Developers

Peter Holden, PhD, Senior Business Development Manager, Licensing and Commercial Supply, Thermo Fisher Scientific, United States

Lyophilization has become increasingly popular among assay developers because it offers advantages in terms of ease of use, shelf life, and ambient temperature shipping and storage. Now, Thermo Fisher Scientific can provide your assay to you in a lyophilized format, ready to ship to your customers. Learn about how you can streamline your supply chain by partnering with us on assay development and manufacturing.

16:20 Refreshment Break in the Exhibit Hall with Poster Viewing

17:00 Breakout Discussions (Visit www.dxinnovationsummit.com/Breakout-Discussions for details)

 

TABLE: The Power of Proteomics in a Post-Genomic World

Moderator: 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

  • Studying drug interactions in vivo
  • A new generation of Precision Clinical Trials (the crucial role of Pathology; optimal specimens for IO trials)
  • Multi-omic data in medicine – how do we make it actionable?

TABLE: Non-Invasive Salivary Diagnostics Tailoring Precision Medicine
Moderator: Chamindie Punyadeera, PhD, Associate Professor, Biomedical Sciences, Queensland University of Technology, Australia

  • Why saliva testing
  • Current saliva tests
  • Future of saliva testing

18:00 Welcome Reception in the Exhibit Hall with Poster Viewing

19:00 Close of Day

WEDNESDAY 20 MAY

BEYOND BLOOD-BASED ASSAYS: UTILIZING OTHER BIOFLUIDS

08:00 Registration and Morning Coffee

09:00 Chairperson’s Remarks

Lorena Diéguez, PhD, Research Group Leader, Medical Devices Research Group, Nano4Health Unit, Life Sciences Department, INL-International Iberian Nanotechnology Laboratory, Portugal

09:05 Optofluidic Systems for High-Throughput Analysis of Cancer Material in Body Fluids: Towards Personalized Medicine

Lorena Diéguez, PhD, Research Group Leader, Medical Devices Research Group, Nano4Health Unit, Life Sciences Department, INL-International Iberian Nanotechnology Laboratory, Portugal

Microfluidics is a powerful tool to control fluids at the microscale. Plasmonics and surface-enhanced Raman scattering spectroscopy can be used for highly sensitive molecule detection. Together, with microfluidics and plasmonics, we can build new technologies for precise isolation of tumor material from body fluids and multiplex biomarker analysis.

09:35 Saliva, Exosomes and Type 2 Diabetes Diagnostics

Christa Noehammer, PhD, Senior Scientist, Molecular Diagnostics, AIT Austrian Institute of Technology GmbH, Austria

Saliva is a readily and, even within short time intervals, repeatedly available body fluid, which can be obtained via non-invasive, painless collection. The Molecular Diagnostics research group at the AIT Austrian Institute of Technology has proven the suitability for circulating biomarker-based saliva diagnostics in a variety of proof-of-concept studies, including DNA-methylation-, miRNA-, protein- and autoantibody-based biomarkers. In the present talk, we will report on results of a research project where we have been looking for salivary and plasma exosome-derived epigenetic biomarkers for early type 2 diabetes diagnosis.

10:05 Identification of Treatment Resistance in Metastatic Prostate Cancer Patients by Leveraging Sequential Plasma Sample Analysis

Daniel Wetterskog, PhD, Senior Research Associate, UCL Cancer Institute, University College London, United Kingdom

The Treatment Resistance Team at the UCL Cancer Institute has been using plasma to interrogate treatment resistance in castration-resistant prostate cancer (CRPC) and develop biomarkers for selecting treatment. Using targeted next-generation sequencing and droplet digital PCR on cfDNA from sequential plasma samples, we have identified markers of response to abiraterone, enzalutamide and chemotherapies. In the presentation, I will discuss our latest findings and ongoing treatment resistance studies.

10:35 Presentation to be Announced

11:05 Coffee Break in the Exhibit Hall with Poster Viewing

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


KEYNOTE SESSION: BRINGING LIQUID BIOPSY

ASSAYS TO THE CLINIC

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.

16:05 Close of Enabling Technologies for Liquid Biopsy and Beyond – Part 1

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2020 CONFERENCE PROGRAMS

19-20 MAY 2020

20-21 MAY 2020