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SELECTBIO Conferences EV-based Diagnostics, Delivery & Therapeutics

EV-based Diagnostics, Delivery & Therapeutics Agenda



Co-Located Conference Agendas

Circulating Biomarkers World Congress 2020 | EV-based Diagnostics, Delivery & Therapeutics | 

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Monday, 17 February 2020

08:00

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


Session Title: Conference Opening Session -- Emerging Themes in Circulating Biomarkers and Exosomes/EVs


Venue: Coronado Ballroom C

08:30

Michael GranerConference Chair

Welcome and Introduction to the Conference
Michael Graner, Associate Professor, Dept of Neurosurgery, University of Colorado Anschutz School of Medicine, United States of America

08:45

Jennifer JonesKeynote Presentation

Liquid Biopsies Using EVs: Promise and Peril on the Frontiers of a New Field
Jennifer Jones, NIH Stadtman Investigator, Head of Transnational Nanobiology, Laboratory of Pathology, Center for Cancer Research, National Cancer Institute, United States of America

09:15

Daniel ChiuKeynote Presentation

New Flow-Based Technologies for the High-Sensitivity and High-Resolution Analysis of CTCs and Exosomes
Daniel Chiu, A. Bruce Montgomery Professor of Chemistry, University of Washington, United States of America

This presentation will describe two flow-based technologies we developed for the analysis of single rare cells and individual extracellular vesicles. The first flow platform is a rare-cell isolation instrument we call eDAR (ensemble decision aliquot ranking), which is capable of operating in a rapid sequential sorting mode for isolating single rare cells with exceptionally high sensitivity and purity. The second flow instrument is a single-vesicle sorter, capable of high-sensitivity analysis of individual extracellular vesicles. I will outline the workings of these new tools, describe their performance, and discuss the clinical questions we are addressing with these next-generation technologies.

09:45

Min YuKeynote Presentation

Circulating Tumor Cells Inform Mechanism of Breast Cancer Metastasis
Min Yu, Assistant Professor, University of Southern California, United States of America

Circulating tumor cells (CTCs) are expected to contain metastasis-initiating cells that can shed light on the mechanisms of cancer metastasis. However, due to limited patient-derived material, the metastatic capability of CTCs has yet to be proved. Using our recently established patient-derived CTC lines, we found that different patient CTC lines demonstrated distinct metastatic tissue tropisms in immunodeficient mice and identified associated pathways to specific organs via RNA-seq and ATAC-seq analysis.

10:15

Morning Coffee Break and Networking in the Exhibit Hall

10:45

Biofluid Biomarkers for the Brain
Kendall Van Keuren-Jensen, Professor and Deputy Director, Translational Genomics Research Institute, United States of America

We will describe some of our efforts in using exRNAs as diagnostics for central nervous system injury and disease.

11:15

John NolanKeynote Presentation

Deciphering the Vesicle Code: Making Sense of EV Heterogeneity
John Nolan, Professor, The Scintillon Institute, United States of America

Cells release extracellular vesicles (EVs) that can carry molecular cargo, including lipids, proteins, and nucleic acids, to nearby or distant cells and affect their function. Understanding the mechanisms of EV biogenesis, uptake and transport has the potential to lead to new biomarkers, diagnostics, and therapeutics. A limit to realizing this potential is the ability to measure individual EVs and their cargo quantitatively and reproducibly. Conventional bulk biochemical analyses, which report only the total amount of cargo in an EV preparation, cannot effectively assess compositional heterogeneity. Single EV analysis methods are required, but conventional tools are challenged to accurately measure small, dim particles. We have developed a vesicle flow cytometry (vFC) method that can detect and size individual EVs to 70 nm, and measure surface cargo to ~25 molecules/EV. vFC allows the identification and characterization of vesicle sub-types within heterogeneous populations in culture supernatants of biofluids. Single EV analysis using vFC reveals striking differences in the expression of canonical vesicle cargo such as tetraspanins, as well as other surface markers including integrins, tumor markers, and carbohydrates on EVs in biofluids and even EVs collected from cultured cell lines. vFC-based single EV immunophenotyping will enable us to understand the origins and functions of EVs in much the same way cell-based immunophenotyping has enabled a detailed understanding of the immune system, and lead to a new generation of EV-based biomarkers, diagnostics, and therapeutics.

11:45

Randolph CortelingKeynote Presentation

An Exosome-based Drug Delivery Platform Derived From an Immortalized Human Neural Stem Cell (hNSC) Line
Randolph Corteling, Head of Research, ReNeuron Ltd., United Kingdom

To ensure the scale required for clinical research and commercialization producer cell immortalization and clonal isolation is a practical strategy to produce consistent, functionally bioactive exosomes for use as therapeutic agents. Immortalization ensures production stability and reduces the need for equivalence testing.

CTX0E03 is a conditionally immortalised human neural stem cell line that has been manufactured to clinical-grade (GMP) standards, using a 3-tier banking strategy and is currently in Phase IIb clinical evaluation for disability after stroke. Using the conditioned media produced during GMP manufacture, we have shown that CTX0E03 is an abundant producer of exosomes that can be readily isolated and purified at scale. The CTX cell line can also be rapidly and efficiently modified to direct the expression of a variety of cargoes within the secreted EV population, whilst maintaining the key immortalised stem cell characteristics of the parental cell line.  The natural tissue tropism of CTX-derived exosomes can then be exploited to deliver loaded cargoes to target cells.

12:15

Susanne GabrielssonKeynote Presentation

Optimizing Dendritic Cell-Derived Exosomes For Cancer Immunotherapy
Susanne Gabrielsson, Professor, Division of Immunology and Allergy, Department of Medicine Solna, Karolinska Institutet, Sweden

Peptide loaded exosomes are promising cancer treatment vehicles, however, low T cell responses in human clinical trials indicate a need to further understand exosome-induced immunity. We previously demonstrated that antigen-loaded exosomes carry whole protein antigens and require B cells for induction of antigen-specific T cells. I will discuss our latest data where we investigated the need for different immune related molecules on exosomes to induce T cell responses and tumor rejection in the B16 mouse melanoma model. Our data demonstrate ways to increase the feasibility of exosome-based therapeutic approaches in cancer.

12:45

Networking Lunch in the Exhibit Hall, Exhibits and Poster Viewing


Session Title: Luncheon Technology Spotlight Sponsored by Clara Biotech
Session SponsorsSession Sponsor

13:15

Luncheon Technology Spotlight Presentation: Advancements in Exosome Isolation: Impacts on Research and Therapeutic Development
Jim West, CEO, Clara Biotech, United States of America
Mei He, Assistant Professor, University of Kansas and Chief Science Officer, Clara Biotech, United States of America

Don’t miss this informative lunch session!

The newest technologies laying the groundwork for future exosome research and commercialization will be discussed, highlighting advancements that will have a far-reaching impact on this burgeoning space.

Exosome isolation, purification, yield and viability are critical to research, biomarker identification and therapeutic development. As the industry learns more, being able to focus on specific exosome subtypes is becoming increasingly important to this growing field.

This seminar will review current and future exosome isolation technologies and platforms, while also discussing their respective impacts on the molecular components of exosomes.

*** Every attendee will get an exclusive conference gift for attending this seminar ***


Session Title: Exosomes and Extracellular Vesicles (EVs) -- Research, Biomarkers, Delivery and Therapeutics Arenas
Session SponsorsSession Sponsor
Session Chair: Behzad Mahdavi, Vice President of Strategic Innovation & Alliances, Lonza, United States of America


Venue: Coronado Ballroom C

14:00

Raghu KalluriKeynote Presentation

Basic and Applied Biology of Exosomes for Diagnosis and Treatment of Cancer
Raghu Kalluri, RE Bob Smith Distinguished Chair in Cancer Research, Chairman - Department of Cancer Biology, MD Anderson Cancer Center, United States of America

14:30

Dominique PV de KleijnKeynote Presentation

Plasma Extracellular Vesicle Sub-fractions as Biomarker Source For Cardiovascular 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 SCAD is challenging, as many patients present with atypical symptoms. 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 plasma extracellular vesicle protein content of vesicles from plasma sub-fractions as an accurate source for early diagnosis of SCAD. This plasma sub-fraction technology is also used for prognosis of a second MI or stroke to identify the high risk patient that can be treated with more intensive and often more costly medication.

15:00

Lucia LanguinoKeynote Presentation

Extracellular Vesicles in Cancer Progression
Lucia Languino, Professor of Cancer Biology, Thomas Jefferson University, United States of America

A variety of studies has shown the role of cancer cell-derived extracellular vesicles (EVs) in tumor progression.  Our and others’ studies have also demonstrated that cancer cell-derived small EVs (sEVs) target multiple recipient cells, such as cancer cells as well as monocytes in the tumor microenvironment (TME).  We have specifically shown that prostate cancer cell-derived sEVs are taken up by cancer cells and monocytes and they are equally efficient in modulating the functions of these cells.  This is expected since tumor growth is supported by all components of the TME and requires monocyte differentiation into a M2 pro-tumorigenic phenotype. We now demonstrate that the alphaV integrins are up-regulated in circulating prostate cancer sEVs, and play a major role in the sEV functions described above.  We demonstrate that de novo alphaV integrins’ expression in TME cells is not caused by increased mRNA levels but rather by sEV-mediated protein transfer.  We have used CRISPR-Cas9 technology and current approaches recommended by MISEV2018 to isolate sEVs lacking alphaVbeta3 or alphaVbeta6 integrins.  We specifically show that in vivo and in vitro sEVs containing these integrins are required to reprogram cancer cells toward a very aggressive neuroendocrine phenotype, or to increase pro-angiogenic activities of microvascular endothelium.  The ability of the alphaVbeta3 and alphaVbeta6 integrins to affect a specific target cell via sEVs appears to be mediated by their unique beta subunit and by activation of specific signaling pathways. Overall, our recent investigations show that the expression of the alphaV integrins in sEVs generates vesicles that have pro-tumorigenic activities.  Thus, we conclude that inhibition of these integrins and their downstream effectors might offer novel therapeutic strategies in prostate cancer.  We also conclude that alphaV integrins in prostate cancer patient sEVs may be a clinically useful and non-invasive biomarker for prostate cancer progression.

15:30

Afternoon Coffee and Tea Break and Networking

16:00

Chulhee ChoiKeynote Presentation

Development of Therapeutic Exosomes: Principles and Applications
Chulhee Choi, Professor and Chair, BioMedical Imaging Center, Korea Advanced Institute of Science and Technology (KAIST), President, ILIAS Biologics Incorporated, Korea South

Our group has recently developed an opto-genetically engineered exosome system, named "exosomes for protein loading via optically reversible protein–protein interaction” (EXPLOR) that can deliver soluble proteins into the cytosol of target cells via controlled, reversible protein–protein interactions (PPI). By integrating a reversible PPI module controlled by specific wavelength of light with the endogenous process of exosome biogenesis, cargo proteins of our interest can be loaded into newly generated exosomes. Protein-loaded exosomes were shown to significantly increase intracellular levels of cargo proteins and their function in recipient cells in both a time- and dose-dependent manner. In this presentation, I will introduce the basic principles of EXPLOR technology and follow-up studies for therapeutic applications.

16:30

Dana LaroccaKeynote Presentation

Extracellular Vesicles as Reprogramming Reagents for induced Tissue Regeneration (iTR)
Dana Larocca, VP Discovery Research, AgeX Therapeutics, United States of America

The global demographic shift toward an older population has created an urgent unmet medical need for effective therapeutics to treat chronic diseases of aging.  Our somatic restriction model views aging as a progressive loss of robust replicative and regenerative potential, initially observed in the developing embryo, that leads to the eventual loss of tissue homeostasis associated with aging.  We are currently assessing the ability of natural and engineered EVs to restore aging adult cells to a younger more regenerative state.  Accordingly, we hypothesized that EVs from young highly regenerative embryonic progenitor cell lines could potentially act as reprogramming reagents to induce regeneration in aging adult cells and tissues.  Toward this end, we have been mining our PureStem library of over 200 highly scalable and clonally pure embryonic progenitor cell lines to identify cellular sources of EVs capable of induced Tissue Regeneration (iTR). Using angiogenesis as a model system of vascular regeneration, we identified embryonic progenitor cell lines that produce EVs capable of stimulating adult endothelial cell migration and tube formation with increased potency compared to EVs from adult cell lines.  We are using comparative transcriptomic analysis of our PureStem library to identify additional candidate cell lines that produce angiogenic EVs. In addition, we identified miRNA cargo associated with increased angiogenic activity that we are currently loading into native exosomes to determine whether they can enhance therapeutic potency. Our data indicate the potential of embryonic progenitor cell lines as a source of natural and engineered EVs for treating cardiovascular disease as well as other degenerative diseases of aging.

17:00

Paul RobbinsKeynote Presentation

Therapeutic Applications of Extracellular Vesicles for Extending Healthspan
Paul Robbins, Professor, Department of Biochemistry, Molecular Biology, and Biophysics, and the Institute on the Biology of Aging and Metabolism, University of Minnesota Medical School, United States of America

A universal characteristic of aging is loss of tissue regenerative potential due to stem cell dysfunction, contributing to the dramatic increase in the risk of morbidity and mortality. We have used both naturally-aged mice and mouse models of accelerated aging to demonstrate that transplantation of young, functional adult stem cells results in an extension of healthspan. In addition, we have demonstrated that stem cell-derived EVs are a key mediator for conferring the observed extension of healthspan by young stem cells.   Progress towards developing clinically-relevant approaches using adult stem cell-derived extracellular vesicles to treat age-related pathologies and extend healthspan will be presented.

17:30

GE Healthcare Life SciencesIsolation and Purification of Extracellular Vesicles: Current Directions
William Whitford, Strategic Solutions Leader, GE Healthcare Life Sciences

When isolating vesicles for therapeutic applications, it’s advantageous to have a very good understanding of diverse individual characteristics of the target subpopulation. There are many reasons for this, including that the three major groups of EVs have been described (and even defined) according to their mechanism of generation: macrovesicles, apoptotic bodies and exosomes. While the latter are often assumed to represent a homogenous population, significant work on exosomes has revealed distinct subpopulations of differing properties.  These properties include physical behaviors in manipulation, and such molecular composition as proteomic and nucleic acid repertoires.  Significantly, these subpopulations have also been reported to mediate differential effects upon recipient cells and tissues. All-in-all, it has been reported that different populations of exosome types may be generated from differing cell and tissue types, culture techniques, isolation strategies, and even the scale of an identified isolation technology.  
 
Furthermore, it has been reported that no individual isolation technique will exquisitely separate any subpopulation from all others.  This is because each characteristic is presented by more than one sub-type. For example, separation based on size solely cannot isolate any of the three major EV groups, since they significantly overlap in size.  For similar reasons no single technology can even isolate any particular sub-type of exosomes.
 
Finally, the impurities to be removed in the production of EV-based pharmaceutical ingredients are primarily free proteins and host cell DNA– but virus and endotoxin must also be considered.  Many isolation and purification process have been described, and the study points to the value of including some sort of specific capture step.  Approaches to this type of purification will be reviewed.

18:00

Behzad MahdaviKeynote Presentation

Exosome, The Next Small Thing: A Winning Strategy To Lead Its Manufacturing and Characterization
Behzad Mahdavi, Vice President of Strategic Innovation & Alliances, Lonza, United States of America

  • Importance of Exosomes in Precision Medicine and Targeted Delivery
  • How expertise and assets in cell manufacturing are essential for Exosome manufacturing  
  • Leverage the exosome-based liquid biopsy, characterization and profiling in therapeutic development manufacturing
  • Cell Therapy Manufacturing + Exosomes Based Liquid Biopsy = A winning combination to lead Exosomes Manufacturing

18:30

Networking Reception with Beer, Wine and a Buffet Dinner in the Exhibit Hall

19:30

Close of Day 1 of the Conference

19:40

Exosomes-EV Training Course in Ballroom A&B [Separate Registration Required to Attend this Training Course]

Tuesday, 18 February 2020

08:00

Morning Coffee, Tea and Pastries in the Exhibit Hall


Session Title: Exosomes and Extracellular Vesicles (EVs) -- Status of the Field 2020 and Emerging Directions


Session Chairperson: Professor Mei He, University of Kansas


Venue: Coronado Ballroom C

08:30

Properties of Exosomes Derived from Primed Mesenchymal Stem Cells
Johnathon Anderson, Assistant Professor, University of California Davis Health, United States of America

Our work involves characterization of the composition of exosomes (pMEX) derived from primed MSCs. Our data indicate that pMEX possess functional in vitro and in vivo therapeutic properties in models of inflammation associated disease.

09:00

Macrophage Exosomes in Atherosclerosis Control
Robert Raffai, Professor, University of California-San Francisco, United States of America

Macrophages are a type of immune cell that display plasticity in inflammatory diseases including atherosclerosis. M1-macrophages contribute to inflammation and atherosclerosis acceleration while M2-macrophages display opposite effects to suppress and even regress atherosclerosis. More recently, macrophages have been shown to produce exosomes that can travel in the circulation and contribute to metabolic disorders including diabetes. But whether they impact atherosclerotic lesion dynamics is currently unknown. Our findings reveal that exosomes produced by M1-macropahges enhance inflammation and atherosclerosis acceleration while those produced by M2-like macrophages exert opposite effects. Thus, macrophage exosomes could serve as biomarkers and effectors of atherosclerosis disease severity and its resolution.

09:30

Engineering Stem Cell-derived EVs For Local Delivery and Therapeutic Applications
Aijun Wang, Associate Professor, Director of Translational Research, Innovation and Entrepreneurship, University of California-Davis, United States of America

Extracellular vesicles (EVs) play a significant role in cell-to-cell communication. In our previous studies, we have confirmed that EVs secreted by placental mesenchymal stem cells (PMSC-EVs) exert significant neuroprotective functions similar in magnitude to live PMSCs. In this presentation, I will discuss what we have learned about PMSC-EVs and the potential mechanisms of action on how PMSC-EVs are protecting neurons. Recently, we have also developed various approaches to improve MSC-EV’s yield and efficacy, and designed biomaterials-based delivery vehicles to improve MSC-EVs stability, retention and targeted delivery. In summary, we are developing and engineering stem cell-derived EVs into a cell-free, off-the-shelf, and easy-to-use therapeutic modality for various disease treatment and regenerative medicine applications.

10:00

Pharmacoengineered Extracellular Vesicles for Therapeutic Applications
Juliane Nguyen, Associate Professor, University of North Carolina at Chapel Hill, United States of America

An increasing number of studies report that mesenchymal stem cell-derived exosomes have regenerative effects. However, the underlying molecular mechanisms of this are poorly characterized. Using microRNA profiling and network analysis, we identified the dominant biological processes and pathways modulated by exosomal miRNAs. Further, to improve upon the intrinsic biological effects of MSC exosomes, we have discovered novel biomaterials that allow highly efficient loading of exosomes with therapeutic cargoes including nucleic acids, paving the way for cell-free therapeutics in many diseases including cardiac regeneration after myocardial infarction.

10:30

Networking Coffee Break in the Exhibit Hall -- Visit Exhibitors and View Posters

11:00

Mei HeKeynote Presentation

High-Throughput Engineering Exosomes For Precision Immunotherapy
Mei He, Assistant Professor, University of Kansas and Chief Science Officer of Clara Biotech, United States of America

Studying extracellular vesicles (EV), particularly exosomes, is holding great promise. With intrinsic molecular payload and biodegradability, molecular engineering of exosomes opens new avenues for mediating cellular responses and developing novel nano-delivery systems in precision immunotherapy. We will report several novel approaches including microfluidic technology and nanotechnology developed in our research group for engineering exosomes as nanodelivery system employed in advancing precision immunotherapy.

11:30

Steven SticeKeynote Presentation

Neural Exosomes - Therapeutic and Drug Delivery Potential in the Treatment of Neurodegenerative Diseases and Stroke
Steven Stice, Co-Founder and Chief Scientific Officer, Aruna Bio; DW Brook Distinguished Professor and Director of the Regenerative Bioscience Center, Georgia Research Alliance Eminent Scholar, University of Georgia, United States of America

Exosomes represent a promising approach to the future treatment of a number of disease states.  Aruna Bio is utilizing the power of exosomes, or nano-sized extracellular vesicles, to target diseased neural cells and facilitate their repair. The company’s lead exosome product, AB126, is derived from a proprietary neural stem cell line. AB126 crosses the blood-brain barrier and harbors unique neurogenic and angiogenic cargos (mRNA, miRNA, and protein), which have anti-inflammatory, neuroregenerative, and neuroprotective effects in multiple models of neurological disease.  Presentation will review data on neural stem cell derived exosomes and their potential both as a therapeutic and as a delivery vehicle.

12:00

Beckman CoulterFlow Cytometry in the Nanoscale: A Review of Guidelines and Standards
Alina Lelic, Marketing Manager, North America, Beckman Coulter

We will discuss the newly released MIFlowCyt-EV standards for reporting flow cytometry EV research and best practices for achieving results that fall in line with these standards.

12:30

Jan LötvallKeynote Presentation

Clinical Translation of Extracellular Vesicle Research
Jan Lötvall, Professor, University of Gothenburg; Founding President of ISEV; Editor-in-Chief, Journal of Extracellular Vesicles, Sweden

Over the last ten to fifteen years, we have seen a massive increase in the understanding of extracellular vesicle (EV) biology and function, primarily based on in vitro models and animal experimentation. Currently, there is a strong push to translate EV science to the clinic, primarily as diagnostic and therapeutic tools. For diagnostics, tests are becoming available primarily for the diagnosis of different types of cancer, and initially RNA or DNA in the vesicles have been used to phenotype and stage disease. However, a significant number of EV-membrane proteins are starting to identify subpopulations of EVs, and these are putative biomarker candidates in different diseases. In this lecture, I will describe a work process to identify EV subpopulations of different human cell- or tissue origin, and present how they can function as biomarkers. Perhaps even more important is the current investments in developing EVs as therapeutics in different diseases. Several venture capital financed startup biotech companies have been established to develop EV therapeutics in diseases such as cancer or rare diseases such as Neiman-Pick type C. Most EV startups focus on delivering different types of cargo to a recipient cell’s cytoplasm, for example a large protein or an siRNA molecule that otherwise would not be taken up in a recipient cell. I will discuss the different therapeutic opportunities with EVs, and present some of our own efforts in developing highly efficient EV-mimetics directly from cell membranes at very high yields. I predict that in the next few years, EV therapeutics will become a clearly established modality as the next generation of biological medicines, and we are likely to see medical revolution evolving before our eyes.

13:00

Networking Lunch in the Exhibit Hall

13:05

Single EV Analysis Workshop -- Principles of EV Analysis
John Nolan, Professor, The Scintillon Institute, United States of America

Attend an on-site workshop covering principles of EV analysis. This 60 minute session will describe guidelines for rigorous EV characterization including an overview of current methods, considerations and controls for generating interpretable data, and a discussion of published guidelines including the new MIFlowCyt-EV manuscript. The workshop will conclude with a hands-on EV analysis lab demonstrating methods for standardized, reproducible measurement of EV size, concentration and cargo by flow cytometry.


Session Title: Single EV Analysis Workshop Sponsored by Cellarcus and Beckman-Coulter
Session SponsorsSession Sponsor


Session Title: Emerging Themes in Exosomes/EV Research, circa 2020


Session Chairperson: Dr. John Ludlow, ZenBio


Venue: Coronado Ballroom C

14:00

My MahoneyKeynote Presentation

miRNA- and Cytokine-Associated Extracellular Vesicles Mediate Squamous Cell Carcinomas
My Mahoney, Professor and Vice Chair, Thomas Jefferson University, United States of America

Extracellular vesicles (EVs) serve as intercellular messengers carrying lipids, proteins, and genetic material that have been shown to play a significant role in many pathological conditions, including cancer. We recently demonstrated that the cadherin desmoglein 2 (Dsg2), a stem cell marker upregulated in many cancers, modulates EV biogenesis in squamous cell carcinomas (SCCs). Here, we show that this process occurs through the endocytic pathway and requires membrane association through protein palmitoylation. In SCC xenograft models, tumor size correlated with EV release and co-treatment with EVs increased xenograft size. To assess the molecular messengers contributing to the pathogenicity of Dsg2-mediated EVs, a cytokine antibody array was employed to show that Dsg2 stimulates release of multiple cytokines known to promote angiogenesis and inflammation, both of which enhance tumor growth. Profiling by RNAseq showed dramatic down-regulation of miRNAs that target those cytokines. These results suggest that intercellular communication through cell-cell adhesion, cytokine release, and secretion of extracellular vesicles are coordinated, critical for tumor growth and development.

14:30

Dolores Di VizioKeynote Presentation

Palmitoyl-Proteomics to Identify Protein Signatures For Large and Small Cancer-derived Extracellular Vesicles in Patient Plasma
Dolores Di Vizio, Professor, Cedars Sinai Medical Center, United States of America

Extracellular vesicles (EVs) are membrane-enclosed nano- and micro-particles that play an important role in cancer progression and have emerged as a promising source of circulating biomarkers. Historically called with various names, depending on the size, cargo, function and cellular and subcellular origin, they are currently categorized in large and small EVs. Our group and others have reported a cancer-specific population of EVs known as large oncosomes that is significantly larger than exosomes-like EVs, and is released by cancer cells during active metastatic migration. Protein S-acylation, also known as palmitoylation, has been proposed as a post-translational mechanism that modulates the dynamics of EV biogenesis and protein cargo sorting. However, technical challenges have limited large-scale profiling of the whole palmitoyl-proteins of EVs. We successfully employed a novel approach that combines low-background acyl-biotinyl exchange (LB-ABE) with label-free proteomics to analyze the palmitoyl proteome of large EVs (L-EVs) and small EVs (S-EVs) from prostate cancer cells and patient plasma. Here we report the first palmitoyl-protein signature of EVs, and demonstrate that L- and S-EVs harbor proteins associated with distinct biological processes and subcellular origin. We identified STEAP1, STEAP2, and ABBC4 as prostate cancer-specific palmitoyl proteins enriched in both EV populations in comparison with the originating cell lines. Importantly, the presence of the above proteins in EVs was significantly reduced upon inhibition of palmitoylation in the producing cells. We also performed additional experiments on a group of patients with metastatic prostate cancer and narrowed down a list of palmitoylated proteins that can be used as biomarkers in plasma. Finally, the palmitoyl-proteome of EVs in patient plasma significantly differed from the palmitoyl-proteome of whole plasma prior to purify EVs. These results suggest that palmitoylation may be involved in the differential sorting of proteins to distinct EV populations and allow for better detection of disease biomarkers.

15:00

Lorraine O’DriscollKeynote Presentation

The Hopes and Hypes of EV-based Diagnostics, Therapeutics and Delivery in Cancer
Lorraine O’Driscoll, Professor in Pharmacology, Trinity College Dublin, Ireland

Increasing evidence indicates that substantial "cargos of information" involved in cell-to-cell communication are transported out of cells and into body fluids via membrane-surrounded vesicles that are then termed extracellular vesicles (EVs). EVs content seems to include proteins, RNAs and DNA. These -collectively termed extracellular vesicles (EVs)- released from cells were originally considered as junk but are now considered to be mini-maps of their cells of origin.

Some EVs are released from healthy cells and are associated with a range of physiological functions. In cancer, studies of cell lines, animal models and serum or plasma from patients and healthy individuals have advocated EVs in a positive light as minimally-invasive diagnostics and predictive biomarkers, based on relative EV quantitative and/or contents.

15:30

Afternoon Coffee Break in the Exhibit Hall and Networking

16:00

Peptides As Disease-Specific Probes For Targeted Drug Delivery
Sazid Hussain, Research Assistant Professor, Sanford Burnham Prebys Medical Discovery Institute, United States of America

Ligand-directed (synaphic) targeting is a therapeutic strategy that makes use of antibodies, peptides, small molecules, or other moieties that bind to molecular receptors specifically expressed in diseased tissues. Screening of phage display libraries in vivo identifies peptides that recognizes molecular changes at the diseased site. This method has been found to be a powerful and unbiased method to discover peptides that specifically home to diseased tissues, such as tumors, atherosclerotic plaques, tissue injuries, and sites of bacterial infection. The combination of nanoparticle delivery with specific tissue targeting peptides provides a particularly powerful means of improving drug delivery. Such a targeting strategy can therefore potentially improve the efficacy of drugs and reduce their side effects.

16:30

Close of Day 2 of the Conference


Add to Calendar ▼2020-02-17 00:00:002020-02-18 00:00:00Europe/LondonEV-based Diagnostics, Delivery and TherapeuticsEV-based Diagnostics, Delivery and Therapeutics in Coronado Island, CaliforniaCoronado Island, CaliforniaSELECTBIOenquiries@selectbiosciences.com