How do we define different subsets of Extracellular Vesicles? How best can we isolate them? What do they contain? How do they function? How can we bring them to the clinic? Seemingly such simple questions, but for specialists and newcomers to this rapidly expanding field alike, there are no obvious answers. At Cambridge Healthtech Institute’s inaugural Extracellular Vesicles conference, immerse yourself in the findings of leading researchers from academia and industry. Addressing challenges and opportunities pertaining to isolation methods, cargo analysis, deduction of originating cell type and target specificity. Receive expert opinion on the mode of action of exosomes and microvesicles, their use as biomarkers and application in precision medicine, therapeutics and drug delivery, without being limited to any one specific therapeutic area.

Final Agenda

Wednesday, June 20

11:00 am Registration Open (America Foyer)

11:45 Enjoy Lunch on Your Own

12:20 pm Dessert and Coffee Break in the Exhibit Hall with Poster Viewing (America Ballroom)

1:00 PLENARY KEYNOTE SESSION
Essex South

2:30 Refreshment Break in the Exhibit Hall with Poster Viewing (America Ballroom)

BIOMARKERS AND THERAPEUTIC TARGETS
Essex Center

3:10 Chairperson’s Opening Remarks

John Pezacki, PhD, Professor, Chemistry and Biomolecular Sciences, University of Ottawa

3:15 Diversity of Extracellular Vesicles - Importance for Biological Function

Jan Lötvall, MD, PhD, Professor, Krefting Research Centre, University of Gothenburg; Senior Consultant, Codiak BioSciences, Inc.

An array of different types of extracellular vesicles (EVs) are released by all cells. These vesicles have the capacity to shuttle both proteins, lipids and nucleotides such as RNA between cells, leading to an array of functional changes in a recipient cell. Importantly, the EV secretome changes significantly in disease, including cancer and inflammation. This lecture will discuss the morphology, cargo and function of different types of EVs, and how their biology has importance for health and disease.

3:45 ADDENDUM Chemical and Biological Modifications to Therapeutic Exosomes

John Pezacki, PhD, Professor, Chemistry and Biomolecular Sciences, University of Ottawa

I will discuss the systematic modifications of microRNA cargo in hepatocyte-derived exosomes in pursuit of therapeutically relevant exosome preparations. Novel strategies for chemical and biochemical modifications of these exosomes will also be discussed, in particular metabolic labeling as well as the use of expanded genetic code methodologies for the site specific modification and control of exosomes.

 4:15 Meet the Nanoimager 

Jonathan Shewring, PhD, Field Application Scientist, ONI

The Nanoimager from ONI is a desktop-compatible, super-resolution, single-molecule fluorescence microscope with localization precision reaching 20 nm. This talk will discuss its key features relevant for life scientists, such as single-molecule localization-based super-resolution, single particle tracking, single-molecule FRET, and SIM, as well as the most recent results.

4:45 Engineered Extracellular Vesicles for CRISPR/Cas9 Gene Editing

Niek Dekker, PhD, Principal Scientist, Discovery Sciences, AstraZeneca

Extracellular vesicles (EVs) represent an exciting opportunity as biological delivery vehicles for therapeutic cargo with excellent safety, low intrinsic immunogenicity, cell-specific tropism and biological delivery efficiency. There are multiple approaches for the introduction of protein and RNA cargo into EVs, including physical, chemical and cell engineering. I will overview a wide range of loading technologies with examples of cell line engineering for both protein and RNA cargo loading.

5:15 The NIH Extracellular RNA Communication Program Towards Biomarker and Therapy Development

Kayla Valdes, PhD, Scientific Program Manager, Office of the Director, Division of Special Initiatives, National Center for Advancing Translational Sciences, National Institutes of Health

Extracellular RNA (exRNA) can act as a signaling molecule, communicating with other cells and carrying information from cell to cell throughout the body. The NIH supports the cross-cutting research towards a better understanding of basic exRNA biology with the goal of improving the diagnosis, prognosis and treatment of various diseases and conditions such as cancer, bone marrow disorders, heart disease, Alzheimer’s disease and multiple sclerosis.

5:45 Close of Day and Dinner Short Course Registration*

*Separate registration required.

Thursday, June 21

7:30 am Registration Open (America Foyer) and Morning Coffee (Foyer)

PRODUCTION AND ENGINEERING
Essex Center

8:00 Chairperson’s Remarks

John Pezacki, PhD, Professor, Chemistry and Biomolecular Sciences, University of Ottawa

8:05 Harnessing the Diversity of Highly Scalable Cell Lines Derived from Human Pluripotent Stem Cells for EV Discovery and Production

Dana Larocca, PhD, Vice President, Discovery Research, AgeX Therapeutics, Inc.

Our diverse cell bank of hundreds of highly scalable and clonally pure pluripotent stem cell-derived progenitor cell lines is an excellent source of cells for EV discovery and therapeutics. We are mining the cell bank using EV content and cell-based assays to screen for desirable EV bioactivities and stably high yields. We successfully identified several candidate production cell lines for manufacturing angiogenic EVs for preclinical studies in cardiovascular disease models.

8:35 Manufacturing of Immunomodulatory Human Umbilical Cord Stem Cell EVs for Clinical Application

Mario Gimona, PhD, Head of Production GMP & Head of Research Program “Nanovesicular Therapeutics”, GMP Unit, Paracelsus Medical University Salzburg

MSC-derived extracellular vesicles (EVs) may have therapeutic effects comparable to their parental cells. Strategies must now be designed to successfully translate EV research and to develop powerful therapies, whilst taking into account the applicable regulations regarding safety and efficacy testing. The identification of the mode of action underlying a suggested potency in each therapeutic approach remains a major challenge to the translational path.

9:05 Edible Plant Exosome-like Nanoparticles for Disease Prevention and Therapy

Huang-Ge Zhang, PhD, Professor, Department of Microbiology & Immunology, University of Louisville

We have developed three generations of edible plant-derived nano-vector (EPNV). The first generation is to co-deliver therapeutic agents without toxicity; the second generation for in vivo targeting to sites of inflammation; and third generation for in vivo targeting to antigen presenting cells (APCs) to elicit host immune responses specifically to kill tumor cells. Therefore, EPNV represents a universally applicable delivery vehicle for targeted delivery of therapeutic agents for personalized therapy.

9:35 Find Your Table and Meet Your Moderator

9:40 Interactive Breakout Discussion Groups

This session features various discussion groups that are led by a moderator/s who ensures focused conversations around the key issues listed. Attendees choose to join a specific group and the small, informal setting facilitates sharing of ideas and active networking.

Best Source of Stem Cell Derived EVs

Paul Robbins, PhD, Professor and Director of the TSRI Center on Aging, Molecular Medicine, The Scripps Research Institute

• Are EVs derived from embryonic stem cells as or more therapeutic than adult stem cells?
• How similar in phenotype and function are the EVs from different stem cell sources?
• Can allogeneic stem cell derived EVs be used clinically?

10:20 Coffee Break in the Exhibit Hall with Poster Viewing (America Ballroom)

11:05 Production of Functionally Bioactive EVs from an Immortalized Human Neural Stem Cell Line and Their Therapeutic Application

Randolph Corteling, PhD, Head of Research, R&D, ReNeuron, Ltd.

To ensure the scale required for clinical research and development, producer cell immortalization and clonal isolation is a practical strategy to produce consistent, functionally bioactive exosomes for use as therapeutic agents. Using the conditioned media produced during GMP manufacture, we have shown that the cell line is an abundant producer of exosomes which can be readily isolated, purified at scale and has demonstrated efficacy in a number of preclinical models.

11:35 Production and Storage Conditions for Therapeutic Extracellular Vesicles

Steven M. Jay, PhD, Assistant Professor, Fischell Department of Bioengineering, University of Maryland

Potential therapeutic applications for extracellular vesicles (EVs) are expanding rapidly. However, fundamental pharmaceutical parameters such as production and storage conditions have yet to be standardized. Here, I will discuss the development and optimization of systems for large-scale production of EVs with therapeutic bioactivity as well as studies on the effects of storage conditions on EV function. Increased understanding of these parameters could enhance translational potential of EV-based therapies.

12:05 ADDENDUM Inflaming the Masses: Glioblastoma EVs Promote Inflammatory Responses, Degradative and Metabolic Alterations in Normal Brain Cells

Michael W. Graner, PhD, Associate Professor, Neurosurgery, University of Colorado Denver, Anschutz Medical Campus

Extracellular vesicles (EVs) from glioblastomas--ultra-lethal brain tumors--manipulate normal brain cells such as astrocytes to promote an inflammatory, pro-tumor microenvironment. This is in addition to extracellular matrix degradation and metabolic changes in brain tissues that likely benefit the tumor. We discuss these dramatic, glioblastoma EV-driven changes in normal cells in the context of our current therapies, and how those treatments may actually contribute to the problems described.

12:35 Networking Luncheon in the Exhibit Hall with Poster Viewing (America Ballroom)

THERAPEUTIC APPLICATION
Essex Center

1:55 Chairperson’s Remarks

John Pezacki, PhD, Professor, Chemistry and Biomolecular Sciences, University of Ottawa

2:00 Cell Entry Routes and Subcellular Fate of Exosomes – Towards Next-Generation Drug Delivery Vehicles

Nicole Meisner-Kober, PhD, Scientific Director, Research Studios Austria, University of Salzburg, Formerly Senior Investigator, Novartis Institutes for Biomedical Research

Current state of the art liposomal delivery vehicles are quantitatively inefficient in delivering siRNA, due to both, limitations in cell entry as well as inefficient subcellular trafficking to the RNA silencing machinery which is nucleated at the rough endoplasmatic reticulum. Since the liposomal vehicles are typically responsible for dose limiting toxicity rather than the active oligonucleotide cargo, an improvement in cellular and subcellular trafficking activity presents a major opportunity for increasing the therapeutic index. In this seminar I will discuss how exosomes have evolved a specific route for cell entry with efficiency and pathways converging with highly infective pathogens, which licenses them for directed subcellular transport to the sites of translation and RNA silencing, and provide a perspective for translation of this biology into next generation RNA and drug delivery strategies.

2:30 Immune Modulation Mechanisms Exerted by Extracellular Vesicles from Umbilical Tissue Mesenchymal Stem Cells

Andrew Hoffman, DVM, DVSc, Diplomate ACVIM, Director of the Regenerative Medicine Laboratory, Professor, Large Animal Medicine, Department of Clinical Sciences, Tufts University Cummings School of Veterinary Medicine

Numerous clinical trials addressing a myriad of disease processes are in progress employing mesenchymal stem cells (MSC), yet the role of extracellular vesicles (EV) in MSC therapeutics is uncertain. Our laboratory examines signaling pathways exerted through EV derived from Wharton’s Jelly MSC. We have found that several classical signaling pathways are largely transduced through the EV fraction of the secretome. These observations have significant implications for development of EV therapeutics.

3:00 Therapeutic Approaches Using Extracellular Vesicles for Treating Age-Related Degenerative Diseases

Paul Robbins, PhD, Professor and Director of the TSRI Center on Aging, Molecular Medicine, The Scripps Research Institute

We have demonstrated that intraperitoneal (IP) administration muscle-derived stem/progenitor cells (MDSPCs) and mesenchymal stem cells isolated from young wild-type mice into mouse models of aging conferred significant lifespan and healthspan extension through a paracrine/endocrine mechanism involving extracellular vesicles (EVs). An update on the use of stem cell EVs as therapeutics for aging and as diagnostics for unhealthy aging will be presented.

3:30 Utilizing Extracellular Vesicles from Patient Plasma to Identify Biomarkers of Autoimmune Disease

Swetha Srinivasan, PhD, Postdoctoral Fellow, Translational Immunology, AbbVie, Inc.

Identifying clinically significant differences in EV-derived RNA is not trivial due to the large inter-individual variability even in healthy individuals as well as the bias and confounding factors introduced by measurement methods. Thus, the initial objective was to assess both the biological and technical variability of EV RNA frequency in healthy individuals. Subsequently, this analysis will enable the identification of exosomal RNA based disease biomarker in autoimmune disorders.

4:00 Close of Conference