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SELECTBIO Conferences EV-based Diagnostics, Delivery & Therapeutics

EV-based Diagnostics, Delivery & Therapeutics Agenda

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Monday, 17 February 2020


The Use of Vesicles from Cow Milk for Oral Drug Delivery
Tom Anchordoquy, Professor, University of Colorado Skaggs School of Pharmacy and Pharmaceutical Sciences, United States of America

Many pharmaceuticals must be administered intravenously due to their poor oral bioavailability.  In addition to issues associated with sterility and inconvenience, the cost of repeated infusion over a six-week course of therapy costs the healthcare system tens of billions of dollars per year.  Attempts to improve oral bioavailability have traditionally focused on enhancing drug solubility and membrane permeability, and the use of synthetic nanoparticles has also been investigated.  As an alternative strategy, some reports have clearly demonstrated that exosomes from cow milk are absorbed from the gastrointestinal tract in humans, and could potentially be used for oral delivery of drugs that are traditionally administered intravenously.  Our results demonstrate that milk exosomes are absorbed from the gut as intact particles that can be modified with ligands to promote retention in target tissues.


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.


Aijun WangKeynote Presentation

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.


Dana LaroccaKeynote Presentation

Title to be Confirmed.
Dana Larocca, VP Discovery Research, AgeX Therapeutics, United States of America


Raghu KalluriKeynote Presentation

Title to be Confirmed.
Raghu Kalluri, Professor & Chairman, Department of Cancer Biology; Olla S. Stribling Distinguished Chair for Cancer Research, MD Anderson Cancer Center, United States of America


Exosomes and Viral Infections: Struggles of the Host Cell with the Intracellular Pathogen
Fatah Kashanchi, Professor, George Mason University, United States of America

In order to perform normal functions, cells release various types of vesicles, such as exosomes and microvesicles (MVs) derived from endosomes and the plasma membrane. These extracellular vesicles (EVs) play a significant role in intercellular communication by serving as a carrier for the transfer of membrane and cytosolic proteins, lipids, and RNA between cells. In recent years, using state of the art technologies such as RNA seq, RPMA, and single cell omics, we have found that virally infected cells including HIV, HTLV, Rift Valley Fever, VEEV, Zika and Ebola virus secret exosomes that contain biomarker of infections. These markers include viral RNA, viral proteins and a range of unique cellular proteins that are released from infected cells. EVs were characterized using electron microscopy, nanoparticle tracking analysis (NTA), and common structural and functional proteins, such as Rab GTPase, SNAREs, annexins, Alix, Tsg101, flotillin and tetraspanins. These exosomes can be found in bodily fluids including urine, saliva, CSF, and blood. Interestingly, these exosomes can be detected during most inhibitory treatments (i.e. IFN, cART) indicating that infected cells may be present and active in tissues reservoirs (i.e. CNS, Lymph nodes). They also contain the usual viral proteins and RNAs and may be part of an early overexpression by these viruses to favor virus gene expression, assembly, and budding.  Therefore, exosomes from infected cells pose a superior predictor of host response biomarker of infection since they contain and protect the viral biomarkers in various bodily fluids. In recent years, the diverse biological cargo contained within certain uninfected stem cell EVs (i.e., iPSC or MSC) are used for repair purposes.  In a series of recent studies using large scale purification methods via tangential flow filtration (TFF), we have isolated iPSCs and MSCs EVs which significantly enhance the processes of cellular migration and angiogenesis in healthy recipient cells.  In models of induced cellular damage (i.e., irradiation or infections), these EVs had the ability to rescue viability in multiple 2D and 3D cultures. Interestingly, there seems to be a “dual” mode of action, where non-coding RNAs activate innate immune molecules followed by presence of cytokines for activation and repair.  Collectively, these results from past few years demonstrate the potential of EVs as diagnostic markers of infection, and stem cell EVs as a “holistic” therapeutic approach to reverse or to reduce cellular damage.


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.


Jan LötvallKeynote Presentation

Title to be Confirmed.
Jan Lötvall, Professor, University of Gothenburg; Founding President of ISEV; Editor-in-Chief, Journal of Extracellular Vesicles, Sweden


Paul RobbinsKeynote Presentation

Title to be Confirmed.
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 Multi-Dimensional Approach to EV Flow Cytometry
Andries Zijlstra, Associate Professor of Pathology, Microbiology and Immunology, Vanderbilt University Medical Center and Vanderbilt Ingram Cancer Center, United States of America

Flow cytometry has proven to be very promising method for Single-EV analysis. Unfortunately, the heterogeneity of EV populations prevents the application of the single-particle classification strategy derived from conventional flow cytometry of intact cells fails in our attempts to resolve distinct classes of EVs. In simple terms, the small size of most EVs prevents the incorporation of all protein markers that define a uniform class of EVs. Consequently, EVs generated through the same biogenesis pathway from the same donor cells, could contain vastly different cargo. Conversely, restricting EV classification only to a size range is equally limiting. To improve EV sub-classification and enable the identification of biologically-significant alterations in EV populations in response to alterations in physiological or pathological states of the donor cell/tissue, we have developed a multi-dimensional approach to EV flow cytometry that attempts to cluster EVs into subpopulations on the basis of many, rather than single parameters.


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.


Samir EL-AndaloussiKeynote Presentation

EV Engineering For Biomedical Applications
Samir EL-Andaloussi, Associate Professor, Karolinska Institutet, Sweden

The presentation will describe work-flows for scalable purification of bioengineered EVs, down-stream vesicular analytics and application of such EVs in therapeutic contexts.


Mei HeKeynote Presentation

High-Throughput Engineering Exosomes For Precision Immunotherapy
Mei He, Assistant Professor, University of Kansas, 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.


Jennifer JonesKeynote Presentation

Title to be Confirmed.
Jennifer Jones, Staff Clinician, Molecular Immunogenetics & Vaccine Research Section, National Cancer Institute (NCI), United States of America


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.


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.


Title to be Confirmed.
Davide Trotti, Professor, Scientific Director, Weinberg ALS Center, Vickie and Jack Farber Institute for Neuroscience, Thomas Jefferson University, United States of America


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.

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