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SELECTBIO Conferences Liquid Biopsies 2019

Liquid Biopsies 2019 Agenda

Co-Located Conference Agendas

Circulating Biomarkers World Congress 2019 | Liquid Biopsies 2019 | 

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Wednesday, 27 March 2019


Conference Registration, Materials Pick-Up, Morning Coffee and Breakfast Pastries

Session Title: Conference Plenary Session -- Emerging Themes in Circulating Biomarkers and Liquid Biopsies

Plenary Session Chairperson: Lucia R. Languino, Ph.D., Professor of Cancer Biology, Thomas Jefferson University


Jennifer JonesKeynote Presentation

Mt-SEA Pipeline: High Throughput Flow Cytometric Analysis of Exosomes in Clinical Biofluids
Jennifer Jones, Staff Clinician, Molecular Immunogenetics & Vaccine Research Section, National Cancer Institute (NCI), United States of America

Because Extracellular Vesicles (EVs) carry surface receptors that are characteristic of their cells of origin, EVs have tremendous potential as non-invasive biomarkers for diagnosis, risk-stratification, treatment selection, and treatment monitoring. We developed a first-in-class pipeline to characterize EV heterogeneity and provide high-sensitivity quantification of informative EVs in biofluids before, during, and after treatment. By combining multiplex assays with high-resolution, single EV flow cytometric methods together into a Mutiplex-to-Single EV Analysis (Mt-SEA) pipeline, we are able to characterize a broad range of relevant EV subsets, while also accurately measuring the concentration of specific EV populations.  Detection of tumor-associated EVs and detection of EV repertoire changes during treatment paves the way to future evaluation of EVs as as biomarkers for use in personalized, adaptive therapies.


Erkki RuoslahtiKeynote Presentation

Disease-Specific Vascular Markers for Cancer, Atherosclerosis and Brain Diseases
Erkki Ruoslahti, Distinguished Professor and Former President, Sanford Burnham Prebys Medical Discovery Institute, United States of America

We study peptides that home to specific targets in the body. We discover the homing peptides by screening phage libraries for peptides that direct homing of phages to the target tissue in vivo. The homing peptides, which usually bind to receptors in the vessels of the target tissue, can be used to selectively deliver diagnostic probes and drugs to the target. The latest development is the discovery of tumor-penetrating peptides. These peptides activate an endocytic bulk transport pathway we have dubbed the CendR pathway, which can enhance the exit from blood and tissue penetration co-administered compounds even without chemical coupling to the peptide (Ruoslahti, Adv Mater. (2012) 24 3747). We have also identified peptides specific for atherosclerotic plaques, accumulate at the site of a brain injury or recognize the blood vessels in Alzheimer’s disease brain. Our homing frequency have an intrinsic biological active I the disease they target. Examples of the peptide discovery process from initial screening to clinical trials will be given.


Coffee Break and Networking in the Exhibit Hall


Cheng-Ho Jimmy LinKeynote Presentation

Customized Circulating Tumor DNA Platform for Cancer Research
Cheng-Ho Jimmy Lin, Chief Scientific Officer, Oncology, Natera, United States of America

We have created a ctDNA assay custom-built for treatment monitoring and minimal residual disease (MRD) assessment. Our methodology identifies 16 unique, clonal, somatic variants individualized to each patient’s tumor, followed by multiplex PCR and ultra-deep sequencing for longitudinal ctDNA analysis of whole blood samples. In this talk, I will be presenting data across four cancer types -  including lung, colorectal, bladder, and breast, and show how determining ctDNA status longitudinally can be important for patient management and decision-making.


Steve SoperKeynote Presentation

Title to be Confirmed.
Steve Soper, Foundation Distinguished Professor, Director, Center of BioModular Multi-scale System for Precision Medicine, Adjunct Professor, Ulsan National Institute of Science & Technology, William H. Pryor Emeritus Chair of Chemistry, The University of Kansas, United States of America


Hollis ClineKeynote Presentation

Exosome Signaling in Brain Development
Hollis Cline, Chair of Neuroscience and Hahn Professor of Neuroscience, The Scripps Research Institute, United States of America

Exosomes are thought to be secreted by all cells in the body and could to be involved in intercellular communication. I will describe experiments in which we tested whether neural exosomes regulate the development of neural circuits and whether exosome-mediated signaling may be aberrant in in vitro models of a neurodevelopmental disorder using human induced pluripotent stem cells (hiPSC) and in vivo rodent models. I will describe results of quantitative proteomic analysis of exosomes. Together our studies indicate that exosomes have the capacity to influence neuron and circuit development.


Networking Lunch in the Exhibit Hall and Poster Viewing

Session Title: Circulating Cell-Free DNA (cfDNA) -- A Valuable Circulating Biomarker for Liquid Biopsy Development


Ultrasensitive Detection of Cancer Using cfDNA Methylation Sequencing
Jasmine Zhou, Professor, University of California-Los Angeles, United States of America

The detection of tumor-derived cell-free DNA in plasma is one of the most promising directions in cancer diagnosis. The major challenge in such an approach is how to identify the tiny amount of tumor DNAs out of total cell-free DNAs in blood. Here we propose an ultrasensitive cancer detection method, termed ‘CancerDetector’, using the DNA methylation profiles of cell-free DNAs. The key of our method is to probabilistically model the joint methylation states of multiple adjacent CpG sites on an individual sequencing read, in order to exploit the pervasive nature of DNA methylation for signal amplification. Therefore, CancerDetector can sensitively identify a trace amount of tumor cfDNAs in plasma, at the level of individual reads. Testing CancerDetector on real plasma data demonstrated its high sensitivity and specificity in detecting tumor cfDNAs. In addition, the predicted tumor fraction showed great consistency with tumor size and survival outcome. Note that all of those testing were performed on sequencing data at low to medium coverage (1× to 10×). Therefore, CancerDetector holds the great potential to detect cancer early and cost-effectively.


Low Coverage, Genome-Wide Sequencing of Cell-Free DNA Enables the Monitoring of Response to Immunotherapy in Cancer Patients
Taylor Jensen, Director, Research and Development, Sequenom (a LabCorp Company), United States of America

Inhibitors of the PD-1/PD-L1/CTLA4 immune checkpoint pathway have revolutionized cancer treatment with a subset of patients showing durable responses; however, challenges remain in the development of biomarkers to predict or monitor response to these therapies.  The use of cell-free DNA (cfDNA) isolated from plasma, or liquid biopsy, provides a promising method for monitoring response.  In contrast to methods that use ultra-deep (>30,000X) targeted sequencing, we will describe a recently completed a proof-of-concept study using low-coverage (~0.3X), genome-wide sequencing of cfDNA to detect tumor-specific copy number alterations.  As part of this study, we have developed a novel metric, the Genome Instability Number (GIN), to monitor response to these drugs throughout treatment.  In a series of case studies, we will describe how the GIN can be used to discriminate clinical response from progression, differentiate progression from pseudoprogression and identify hyperprogressive disease.  In addition, we have utilized this metric to provide evidence for a delayed pharmacokinetic response for checkpoint inhibitors relative to targeted therapies.


Ultra-Sensitive Mutational Analysis in Cell-Free DNA by Digital PCR and NGS Technologies
Rachel Tam, Senior Scientific Researcher, Oncology Biomarker Development, Genentech, United States of America

Circulating cell-free DNA (cfDNA) in plasma offers a non-invasive approach to monitor tumor molecular profiling in real-time at multiple time-points, detection of emerging genomic alterations associated with drug resistance and clarifying cancer prognosis and diagnosis of cancer recurrence or progression. We developed an ultra-sensitive droplet digital PCR (ddPCR) approach and molecular tagged NGS technologies to detect actionable cancer biomarkers in cfDNA.


Afternoon Coffee Break in the Exhibit Hall


cfDNA Analysis in ALK-positive NSCLC Patients and Potential Clinical Utility
Jean-François Martini, Sr. Director, Translational Oncology, Immuno-Oncology, Early Development, Pfizer, United States of America

Lorlatinib exhibited antitumor activity across a variety of ALK kinase domain resistance mutations, including the difficult-to-treat ALK G1202R mutation. Responses to lorlatinib were also seen in patients resistant to prior ALK TKIs and without detectable ALK resistance mutations in plasma.


Monitoring Recurrence With Personalized ctDNA Assays
Bernhard Zimmermann, Vice President of Research and Development, Natera, United States of America

Signatera™ RUO is the first individualized pan-cancer circulating tumor DNA platform. I will be showing results of validation studies for monitoring treatment response, detecting minimal residual disease and predicting disease recurrence. The test detects tumor DNA down to 0.01% VAF (tumor fraction) and data from clinical studies in lung cancer, bladder cancer, colorectal cancer and breast cancer show that ctDNA is detected in plasma of patients up to over one year ahead of clinical detection of relapse.


Networking Reception with Beer and Wine in the Exhibit Hall


Close of Day 1 of the Conference.

Thursday, 28 March 2019


Morning Coffee and Breakfast Pastries Served in the Exhibit Hall

Session Title: Liquid Biopsy Development for Cancer


Filip JankuKeynote Presentation

Liquid Biopsies – A New Tool in the Personalized Cancer Therapy Toolbox
Filip Janku, Associate Professor, Center Medical Director, Clinical and Translational Research Center, The University of Texas MD Anderson Cancer Center, United States of America

In the era of precision medicine, the optimal choice of cancer therapy depends upon analysis of the tumor genome. The spatial and temporal intratumor heterogeneity of cancers creates substantial challenges, as molecular profile depends on time and site of tumor tissue collection. Molecular analysis of liquid biopsies offers a novel, minimally invasive method that can be performed at multiple time-points and plausibly represents the prevailing molecular profile of the cancer. Molecular analysis of liquid biopsies offers multiple clinically useful applications, such as identification of molecular targets for cancer therapy, monitoring of tumor molecular profile in real time, detection of emerging molecular aberrations associated with resistance to particular therapy, determination of cancer prognosis and cancer recurrence or progression.


Hatim HusainKeynote Presentation

Circulating Tumor DNA Analyses in Lung Cancer
Hatim Husain, Assistant Professor of Medicine, University of California San Diego, United States of America

We will explore current approaches to the implementation of ctDNA strategies in clinical care. Topics that will be discussed are utility studies in early detection, disease monitoring, and monitoring response.


Coffee Break and Networking in the Exhibit Hall


Sam HanashKeynote Presentation

Multi-Omic Liquid Biopsy Platform
Sam Hanash, Director, McCombs Institute for Cancer Detection and Treatment, University of Texas MD Anderson Cancer Center, United States of America

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.


Networking Lunch in the Exhibit Hall and Poster Viewing


Quantitative Detection of Gene Rearrangements Using Circulating Tumor Cells Purified by a Covalent Chemistry-Enabled Platform
Yazhen Zhu, Assistant Project Scientist, David Geffen School of Medicine at UCLA, United States of America

Recent research focus in the field of circulating tumor cells (CTCs) has moved beyond the simple capture or enumeration of CTCs and gravitated towards approaches that allow for in-depth molecular analysis. Unlike circulating tumor DNA or RNA which is highly fragmented and compounded by significant background, CTCs house intact genomic DNA and RNA,providing more reliable genetic information about tumors. Exploring the use of CTC-derived mRNA offers a non-invasive diagnostic solution for understanding underlying tumor biology, guiding treatment intervention, and monitoring disease progression. Recently, we demonstrated a new covalent chemistry-enabled CTC capture/release platform – “Click Chip”. This platform is designed by integrating bioorthogonal ligation-mediated CTC capture (sensitive and rapid) and disulfide cleavage-driven CTC release (mild, specific, and rapid) on nanostructured substrates to enable more efficient purification of pooled CTCs with high-quality intact CTC-derived mRNA. The CTC-derived mRNA was subjected to RT-droplet digital PCR (RT-ddPCR). ALK/ROS1 rearrangements were quantified using CTC-mRNA recovered by Click Chips and matched with those identified in biopsy specimen in late-stage ALK/ROS1 positive NSCLC patients. Moreover, copy numbers of ALK/ROS1 rearrangements in CTCs and CTC counts could be used together for evaluating ALK/ROS1-TKI treatment responses and disease progression. This streamlined diagnostic workflow is optimum for gene rearrangement detection and quantification based on high-quality intact CTC-derived mRNA.


David HoonKeynote Presentation

New Molecular Approaches of Blood Biopsy To Monitor Melanoma Patients Progression During Treatment
David Hoon, Professor, Director Department of Translational Molecular Medicine, John Wayne Cancer Institute, United States of America

Will present new platforms to assess blood biopsy in melanoma patients receiving therapy. New approaches in assessing the utility of CTC and cfNA detection.


John PalmaKeynote Presentation

Title to be Confirmed.
John Palma, Chief Medical Officer, Roche Sequencing Solutions, United States of America


Afternoon Coffee Break in the Exhibit Hall


Lydia SohnKeynote Presentation

Title to be Confirmed.
Lydia Sohn, Professor, Department of Mechanical Engineering, University of California, Berkeley, United States of America


Circulating Tumor DNA Methylation Markers for Diagnosis and Prognosis of Hepatocellular Carcinoma
Kang Zhang, Founding Director, Institute for Genomic Medicine, University of California-San Diego, United States of America

We identified an HCC-specific methylation marker by comparing HCC tissue and normal blood leukocytes and showed that methylation profiles of HCC tumor DNA and matched plasma ctDNA are highly correlated. We constructed a diagnostic prediction model with high diagnostic specificity and sensitivity and was highly correlated with tumor burden, treatment response, and stage. Additionally, we constructed a prognostic prediction model that effectively predicted prognosis and survival.


Balaji PanchapakesanKeynote Presentation

Circulating Biomarkers: The New Nanotube-CTC-Microarray Chip for Clinical Impact
Balaji Panchapakesan, Professor, Department of Mechanical Engineering, Worcester Polytechnic Institute (WPI), United States of America

The ability to detect cancer and its heterogeneity non-invasively in the earliest of stages can make a significant clinical impact. Therefore, biopsy of blood and other bodily fluids also called “liquid biopsy” is an emerging concept for non-invasive detection as opposed to surgical methods. Circulating biomarkers is a rapidly growing field of research. Circulating biomarkers include, circulating tumor cells (CTCs), exosomes, circulating tumor DNA (ctDNA), cell-free DNA and RNA (mRNA, miRNA, non-coding RNA, and other RNAs), circulating proteins and metabolites. There are over 400 different methods to capture and analyze circulating biomarkers. However, the clinical impacts of liquid biopsy are yet to be realized. We describe the nanotube-CTC-chip for capture and analysis of circulating tumor biomarkers. Using a micro-array technology, well established in the clinical domain, and utilizing nanosurfaces, we demonstrate the capture and isolation of invasive CTCs, CTC clusters and metastasis initiating cells (MICs). Further, these micro-arrays could be used with little modification to capture exosomes, ctDNA, cfDNA and other protein biomarkers in a single chip. One can also develop nanosequencing techniques using these micro-arrays suggesting a standardized platform for liquid biopsies.


Close of Day 2 of the Conference.

Friday, 29 March 2019


Morning Coffee and Breakfast Pastries Served in the Exhibit Hall

Session Title: Late-Breaking Session


Highly Sensitive Direct Quantification of cfmiRNAs for Biomarker Profiling by Next Generation Sequencing (NGS)
Sergio Barberan-Soler, Director of Sequencing Technologies, Somagenics, Inc, United States of America

Inefficient and inaccurate profiling of microRNAs from biofluids has hindered their usage as biomarkers. We have developed accurate library preparation technologies to profile microRNAs directly from biofluid samples.


Title to be Confirmed.
Victor Ugaz, Professor & Holder of the Charles D. Holland ’53 Professorship, Artie McFerrin Department of Chemical Engineering, Texas A&M University, United States of America


BloodPAC: Establishing Standards to Accelerate Development and Approval of Liquid Biopsy Technology
Lauren Leiman, Executive Director, Blood Profiling Atlas in Cancer (BloodPAC), United States of America

The Blood Profiling Atlas in Cancer (BloodPAC) looks to improve outcomes for patients with cancer through a collaborative infrastructure that enables the sharing of information between stakeholders in industry, academia and regulatory agencies. The goals of BloodPAC are: to aggregate, make freely available, and harmonize for further analysis: i) data from CTC, ctDNA, proteins including tumor associated autoantibodies, and exosome assays, ii) associated clinical data, and iii) sample collection, preparation and handling protocols.


Toward Perfect Detection of Un-amplified Biomarkers with Single-Molecule Kinetic Fingerprinting
Alexander Johnson-Buck, Research Assistant Professor, University of Michigan, United States of America

Conventional techniques for detecting rare DNA and RNA sequences require many cycles of PCR amplification for high sensitivity and specificity, potentially introducing significant biases and errors. In addition, some classes of biomarkers, such as epigenetic modifications and proteins, cannot be amplified directly. While amplification-free methods exist, they rarely achieve single-molecule sensitivity; furthermore, even when such sensitivity is achieved, the ability of most methods to discriminate between single-nucleotide variants is often dictated by the specificity limits of hybridization thermodynamics and/or nonspecific binding of probes to assay surfaces. We show that a direct detection approach using single-molecule kinetic fingerprinting can surpass the thermodynamic discrimination limit by three orders of magnitude.  This approach detects mutations as subtle as the drug resistance-conferring cancer mutation EGFR T790M (a single C>T substitution) with an estimated specificity of 99.99999%, surpassing the single-base selectivity of leading PCR-based methods and enabling detection of 1 mutant molecule in a background of at least 1 million wild-type molecules. This level of specificity revealed rare, heat-induced cytosine deamination events that introduce false positives in PCR-based detection, but which can be overcome in our approach through milder thermal denaturation and enzymatic removal of damaged nucleobases. Using super-resolution analysis methods, the dynamic range of the technique is increased to approximately five orders of magnitude, comparable to that of droplet digital PCR. We also explore methods of increasing sensitivity in surface binding assays through rational engineering of mass transfer to the imaging surface, and in some cases achieve detection limits in the low attomolar range, an improvement of >50-fold relative to passive diffusion alone. These results suggest the utility of single-molecule kinetic measurements for the direct, digital detection of nucleic acids and other analytes with extremely high specificity.


Title to be Confirmed.
Brian Dougherty, Executive Director, Translational Genomics, Oncology IMED, AstraZeneca R&D, United States of America

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