Exosome Diagnosis Presents a Novel Platform for Liquid Biopsy
Takahiro Ochiya, Professor, Department of Molecular and Cellular Medicine, Tokyo Medical University, Japan

Exosomes are 50-150 nm size in diameter extracellular vesicles (EVs) secreted by multiple living cells into the extracellular space. They contain tissue or cell-specific bioactive materials, including DNAs, mRNAs, ncRNAs, proteins, lipids, metabolites, etc. with their specific surface markers, such as, CD9, CD63, CD81, Alix, etc. Exosomes have been considered as information carriers in cell communication between cancer cells and non-cancer cells, which affect gene expressions and cellular signalling pathways of recipient cells by delivering their contents. Exosomes are promising tools for improving cancer care, but conversely may also contribute to tumor progression. Here, we highlight recently discovered roles of exosomes in modulating cancer microenvironment. We also discuss how exosomes could be exploited as biomarkers for a novel platform of liquid biopsy and delivery vehicles in cancer therapy.

Diagnostic Potential of Plasma Vesicles for Ischemic Heart Disease
Dominique PV de Kleijn, Professor Experimental Vascular Surgery, Professor Netherlands Heart Institute, University Medical Center Utrecht, The Netherlands, Netherlands

Cardiovascular Disease (CVD) is with the cardiovascular events of Ischemic Heart Disease and Stroke, the number 1 and 2 cause of death in the world and expect to increase especially in Asia. Ischemic heart disease (IHD) comprises 3 entities: stable coronary artery disease (SCAD), unstable angina (UA) and myocardial infarction (MI). Because IHD is associated with an increased risk of adverse clinical events such as heart failure and death, early recognition of IHD is of utmost importance. However, to diagnosis IHD is challenging, as many patients present with atypical symptoms. It is known that women have a different symptom sensation than men. Troponins are the main diagnostic tool for detection of MI. Blood biomarkers for SCAD (typically causing stable angina) and UA, however, are not available. These diagnoses frequently require hospital visits/admissions for time-consuming and costly (non)invasive tests. We use a protein signature measured  in 3 different subsets of plasma extracellular vesicle as an accurate source for early diagnosis of SCAD and UA. Diagnosis of ischemic heart disease as well as normalization and characterization of extracellular vesicles in plasma subfractions will be discussed.

Early Assessment of Treatment Response in Solid Tumors via Quantitating Circulating Tumor DNA
Max Ma, Director, Medical Affairs, Roche Sequencing Solutions, Inc., United States of America

Thanks to the advancement of modern medicine, multiple therapeutic options often exist for the treatment of various cancers. Lessons learned from managing blood cancers under therapy have taught us the importance of early response. Longitudinal monitoring of circulating tumor DNA (ctDNA) is an emerging method for disease management in solid tumors. We employed a 197-gene NGS assay, the AVENIO ctDNA Surveillance Kit, which allowed us to perform longitudinal ctDNA analysis and measure changes in ctDNA levels in plasma. Specifically, we evaluated the association between change in ctDNA levels within first two cycles of treatment and survival data from a cohort of 106 advanced lung adenocarcinoma subjects treated with first-line chemo or chemoradiation therapies. Our data show that a decrease in post-treatment ctDNA level measured by the Surveillance Kit was associated with better outcome (both PFS and OS) in advanced lung adenocarcinoma. Thus, an early assessment of treatment effect can be measured using ctDNA in plasma within 1 or 2 treatment cycles.

NanoVelcro Rare-Cell Assays for Detection and Characterization of Circulating Tumor Cells
Hsian-Rong Tseng, Professor, Crump Institute for Molecular Imaging, California NanoSystems Institute, University of California-Los Angeles, United States of America

Circulating tumor cells (CTCs) are cancer cells shredded from either a primary tumor or a metastatic site and circulate in the blood as the potential cellular origin of metastasis. By detecting and analyzing CTCs, we will be able to noninvasively monitor disease progression in individual cancer patients and obtain insightful information for assessing disease status, thus realizing the concept of “tumor liquid biopsy”. Over the past decade, our research team at UCLA pioneered a unique concept of “NanoVelcro” cell-affinity substrates, in which CTC capture agent-coated nanostructured substrates were utilized to immobilize CTCs with remarkable efficiency. Five generations of NanoVelcro CTC assays have been developed over the past decade for a variety of clinical utilities, including CTC enumeration for prognosis and staging, single-CTC mutational analysis for tracking tumor origin, and CTC-based molecular analysis for treatment monitoring.  In this presentation, I will summarize the development of the new generations of NanoVelcro CTC assays and the clinical applications of these new diagnostic devices.

Integrating Aptamer Technology with Paper-Based Point-of-Care Devices for Biomedical Monitoring
John Brennan, Professor and Director, Biointerfaces Institute, McMaster University, Canada

DNA aptamers and DNA enzymes (denoted as functional nucleic acids or FNA) are an emerging platform for development of point-of-care (POC) diagnostic devices.  In this presentation, I will first focus on the development of new aptamers and DNA enzymes for a range of key biomarkers and their integration into colorimetric and fluorimetric assays for a variety of targets, mainly in the area of infectious disease.  Methods to couple target binding to FNAs to produce a DNA strand as an output, and to then use the output DNA to initiate isothermal amplification (ITA), will then be described.  Finally, the printing of specific “modules” for recognition (FNA), amplification (via ITA) and detection onto paper devices will be described as a way to generate a range of new POC devices that allow facile detection of a range of clinical analytes.  Examples will be provided to demonstrate multi-step reactions on paper for ultra-sensitive detection of E. coli, C. difficile, MRSA and H. pylori.

Liquid Biopsy Using the Nanotube-CTC-Chip
Balaji Panchapakesan, Professor, Department of Mechanical Engineering, Worcester Polytechnic Institute (WPI), United States of America

In the recent past, we reported the nanotube-CTC-chip for rapid classification of biomarkers using electrical signals and cell capture from droplets with 55-100% yield. In this talk, we will outline the further development of the nanotube-CTC-chip for highly efficient capture of CTCs with very high quality.  Advantages of the nanotube-CTC-chip include both positive and negative selection strategy on the same chip resulting in potential to capture invasive CTC phenotypes with diverse population of cells. The nanotube-CTC-chip also enables culturing of cancer cells directly on the device for further analysis. Potentially one can achieve capture of CTCs based on multiple biomarkers, negative selection by depleting leukocytes, and density gradient based selection of nucleated cells, thereby avoiding loss of CTCs due to variation in size and biomarker composition in a single blood test.