Journal of Extracellular Vesicles (Dec 2015)
Applying extracellular vesicles based therapeutics in clinical trials – an ISEV position paper
- Thomas Lener,
- Mario Gimona,
- Ludwig Aigner,
- Verena Börger,
- Edit Buzas,
- Giovanni Camussi,
- Nathalie Chaput,
- Devasis Chatterjee,
- Felipe A. Court,
- Hernando A. del Portillo,
- Lorraine O'Driscoll,
- Stefano Fais,
- Juan M. Falcon-Perez,
- Ursula Felderhoff-Mueser,
- Lorenzo Fraile,
- Yong Song Gho,
- André Görgens,
- Ramesh C. Gupta,
- An Hendrix,
- Dirk M. Hermann,
- Andrew F. Hill,
- Fred Hochberg,
- Peter A. Horn,
- Dominique de Kleijn,
- Lambros Kordelas,
- Boris W. Kramer,
- Eva-Maria Krämer-Albers,
- Sandra Laner-Plamberger,
- Saara Laitinen,
- Tommaso Leonardi,
- Magdalena J. Lorenowicz,
- Sai Kiang Lim,
- Jan Lötvall,
- Casey A. Maguire,
- Antonio Marcilla,
- Irina Nazarenko,
- Takahiro Ochiya,
- Tushar Patel,
- Shona Pedersen,
- Gabriella Pocsfalvi,
- Stefano Pluchino,
- Peter Quesenberry,
- Ilona G. Reischl,
- Francisco J. Rivera,
- Ralf Sanzenbacher,
- Katharina Schallmoser,
- Ineke Slaper-Cortenbach,
- Dirk Strunk,
- Torsten Tonn,
- Pieter Vader,
- Bas W. M. van Balkom,
- Marca Wauben,
- Samir El Andaloussi,
- Clotilde Théry,
- Eva Rohde,
- Bernd Giebel
Affiliations
- Thomas Lener
- Spinal Cord Injury & Tissue Regeneration Center Salzburg (SCI-TReCS), Paracelsus Medical University (PMU), Salzburg, Austria
- Mario Gimona
- Spinal Cord Injury & Tissue Regeneration Center Salzburg (SCI-TReCS), Paracelsus Medical University (PMU), Salzburg, Austria
- Ludwig Aigner
- Spinal Cord Injury & Tissue Regeneration Center Salzburg (SCI-TReCS), Paracelsus Medical University (PMU), Salzburg, Austria
- Verena Börger
- Institute for Transfusion Medicine, University Hospital Essen, University of Duisburg-Essen, Essen, Germany
- Edit Buzas
- Department of Genetics, Cell- and Immunobiology, Semmelweis University, Budapest, Hungary
- Giovanni Camussi
- Molecular Biotechnology Center, Department of Medical Sciences, University of Turin, Turin, Italy
- Nathalie Chaput
- Laboratory of Immunomonitoring in Oncology, UMS 3655 CNRS/US23 Inserm, Villejuif, France
- Devasis Chatterjee
- Division of Hematology & Oncology, Rhode Island Hospital, Providence, RI, USA
- Felipe A. Court
- Department of Physiology, Faculty of Biology, Pontificia-Universidad Católica de Chile, Santiago, Chile
- Hernando A. del Portillo
- ICREA at Barcelona Centre for International Health Research (CRESIB), Hospital Clínic – Universitat de Barcelona, Barcelona, Spain
- Lorraine O'Driscoll
- School of Pharmacy and Pharmaceutical Sciences, Trinity College Dublin, Dublin 2, Ireland;
- Stefano Fais
- Anti-Tumor Drugs Section, Department of Therapeutic Research and Medicines Evaluation, National Institute of Health (ISS), Rome, Italy
- Juan M. Falcon-Perez
- Metabolomics Unit, CIC bioGUNE, CIBERehd, Bizkaia Technology Park, Derio, Spain
- Ursula Felderhoff-Mueser
- Department of Paediatrics I, Neonatology, University Hospital Essen, University Duisburg-Essen, Essen, Germany
- Lorenzo Fraile
- Departament de Producció Animal, ETSEA, Universitat de Lleida, Lleida, Spain
- Yong Song Gho
- Department of Life Sciences, Pohang University of Science and Technology, Pohang, Republic of Korea
- André Görgens
- Institute for Transfusion Medicine, University Hospital Essen, University of Duisburg-Essen, Essen, Germany
- Ramesh C. Gupta
- Department of Pharmacology and Toxicology, University of Louisville, Louisville, KY, USA
- An Hendrix
- Laboratory of Experimental Cancer Research, Department of Radiation Oncology and Experimental Cancer Research, Ghent University Hospital, Ghent, Belgium
- Dirk M. Hermann
- Department of Neurology, University Hospital Essen, University of Duisburg-Essen, Essen, Germany
- Andrew F. Hill
- Department of Biochemistry and Genetics, La Trobe Institute for Molecular Science, La Trobe University, Melbourne, Australia
- Fred Hochberg
- Massachusetts General Hospital, Boston, MA, USA
- Peter A. Horn
- Institute for Transfusion Medicine, University Hospital Essen, University of Duisburg-Essen, Essen, Germany
- Dominique de Kleijn
- Department of Surgery, YLL School of Medicine, NUS, Singapore, Singapore
- Lambros Kordelas
- Department of Bone Marrow Transplantation, University Hospital Essen, University of Duisburg-Essen, Essen, Germany
- Boris W. Kramer
- Experimental Perinatology/Neonatology, School of Mental Health and Neuroscience, School of Oncology and Developmental Biology, Maastricht University Medical Center, Maastricht, The Netherlands
- Eva-Maria Krämer-Albers
- Molecular Cell Biology and Focus Program Translational Neurosciences, University of Mainz, Mainz, Germany
- Sandra Laner-Plamberger
- Spinal Cord Injury & Tissue Regeneration Center Salzburg (SCI-TReCS), Paracelsus Medical University (PMU), Salzburg, Austria
- Saara Laitinen
- Research and Cell Services, Finnish Red Cross Blood Service, Helsinki, Finland
- Tommaso Leonardi
- Division of Stem Cell Neurobiology, Department of Clinical Neurosciences, Wellcome Trust-Medical Research Council Stem Cell Institute, University of Cambridge, Cambridge, UK
- Magdalena J. Lorenowicz
- Department of Cell Biology, Center for Molecular Medicine, University Medical Center, Utrecht, The Netherlands
- Sai Kiang Lim
- Institute of Medical Biology, Agency for Science Technology and Research (A*STAR), Singapore, Singapore
- Jan Lötvall
- Krefting Research Centre, Institute of Medicine, the Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden
- Casey A. Maguire
- Harvard Medical School, Massachusetts General Hospital, Boston, MA, USA
- Antonio Marcilla
- Dpto. Biología Celular y Parasitologia, Facultat de Farmacia, Universitat de Valencia, Valencia, Spain
- Irina Nazarenko
- Institute for Environmental Health Sciences and Hospital Infection Control Medical Center, University of Freiburg, Freiburg im Breisgau, Germany
- Takahiro Ochiya
- Division of Molecular and Cellular Medicine, National Cancer Center Research Institute, Tokyo, Japan
- Tushar Patel
- Departments of Transplantation and Cancer Biology, Mayo Clinic, Jacksonville, FL, USA
- Shona Pedersen
- Centre for Cardiovascular Research, Department of Clinical Biochemistry, Aalborg University Hospital, Aalborg University, Aalborg, Denmark
- Gabriella Pocsfalvi
- Mass Spectrometry and Proteomics, Institute of Biosciences and BioResources, National Research Council of Italy, Naples, Italy
- Stefano Pluchino
- Division of Stem Cell Neurobiology, Department of Clinical Neurosciences, Wellcome Trust-Medical Research Council Stem Cell Institute, University of Cambridge, Cambridge, UK
- Peter Quesenberry
- Division of Hematology & Oncology, Rhode Island Hospital, Providence, RI, USA
- Ilona G. Reischl
- BASG – Bundesamt für Sicherheit im Gesundheitswesen – Federal Office for Safety in Health Care, AGES – Agentur für Gesundheit und Ernährungssicherheit – Austrian Agency for Health and Food Safety, Institut Überwachung – Institute Surveillance, Wien, Austria
- Francisco J. Rivera
- Institute of Molecular Regenerative Medicine, Spinal Cord Injury & Tissue Regeneration Center Salzburg (SCI-TReCS), Paracelsus Medical University (PMU), Salzburg, Austria;
- Ralf Sanzenbacher
- Ralf Sanzenbacher, Paul-Ehrlich-Institut, Bundesinstitut für Impfstoffe und biomedizinische Arzneimittel, Federal Institute for Vaccines and Biomedicines, Langen, Germany
- Katharina Schallmoser
- Spinal Cord Injury & Tissue Regeneration Center Salzburg (SCI-TReCS), Paracelsus Medical University (PMU), Salzburg, Austria
- Ineke Slaper-Cortenbach
- Cell Therapy Facility, Department of Clinical Pharmacy, University Medical Center Utrecht, Utrecht, The Netherlands
- Dirk Strunk
- Experimental & Clinical Cell Therapy Institute, Spinal Cord Injury & Tissue Regeneration Center Salzburg (SCI-TReCS), Paracelsus Medical University, Salzburg, Austria
- Torsten Tonn
- Institute for Transfusion Medicine Dresden, German Red Cross Blood Donation Service North-East, Dresden, Germany
- Pieter Vader
- Laboratory of Clinical Chemistry and Hematology, University Medical Center Utrecht, Utrecht, The Netherlands
- Bas W. M. van Balkom
- Department of Nephrology and Hypertension, University Medical Center Utrecht, Utrecht, The Netherlands
- Marca Wauben
- Department of Biochemistry and Cell Biology, Faculty of Veterinary Medicine, Utrecht University, Utrecht, The Netherlands
- Samir El Andaloussi
- Department of Physiology, Anatomy and Genetics, University of Oxford, Oxford, UK
- Clotilde Théry
- Centre of Clinical Investigation in Biotherapy CICBT 1248, Institut Gustave Roussy, Villejuif, France
- Eva Rohde
- Spinal Cord Injury & Tissue Regeneration Center Salzburg (SCI-TReCS), Paracelsus Medical University (PMU), Salzburg, Austria
- Bernd Giebel
- Institute for Transfusion Medicine, University Hospital Essen, University of Duisburg-Essen, Essen, Germany
- DOI
- https://doi.org/10.3402/jev.v4.30087
- Journal volume & issue
-
Vol. 4,
no. 0
pp. 1 – 31
Abstract
Extracellular vesicles (EVs), such as exosomes and microvesicles, are released by different cell types and participate in physiological and pathophysiological processes. EVs mediate intercellular communication as cell-derived extracellular signalling organelles that transmit specific information from their cell of origin to their target cells. As a result of these properties, EVs of defined cell types may serve as novel tools for various therapeutic approaches, including (a) anti-tumour therapy, (b) pathogen vaccination, (c) immune-modulatory and regenerative therapies and (d) drug delivery. The translation of EVs into clinical therapies requires the categorization of EV-based therapeutics in compliance with existing regulatory frameworks. As the classification defines subsequent requirements for manufacturing, quality control and clinical investigation, it is of major importance to define whether EVs are considered the active drug components or primarily serve as drug delivery vehicles. For an effective and particularly safe translation of EV-based therapies into clinical practice, a high level of cooperation between researchers, clinicians and competent authorities is essential. In this position statement, basic and clinical scientists, as members of the International Society for Extracellular Vesicles (ISEV) and of the European Cooperation in Science and Technology (COST) program of the European Union, namely European Network on Microvesicles and Exosomes in Health and Disease (ME-HaD), summarize recent developments and the current knowledge of EV-based therapies. Aspects of safety and regulatory requirements that must be considered for pharmaceutical manufacturing and clinical application are highlighted. Production and quality control processes are discussed. Strategies to promote the therapeutic application of EVs in future clinical studies are addressed.
Keywords
