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Applying extracellular vesicles based therapeutics in clinical trials – an ISEV position paper

Lener, Thomas, Gimona, Mario, Aigner, Ludwig, Börger, Verena, Buzas, Edit, Camussi, Giovanni, Chaput, Nathalie, Chatterjee, Devasis, Court, Felipe A., del Portillo, Hernando A., O'Driscoll, Lorraine, Fais, Stefano, Falcon‐Perez, Juan M., Felderhoff‐Mueser, Ursula, Fraile, Lorenzo, Gho, Yong Song, Görgens, André, Gupta, Ramesh C., Hendrix, An, Hermann, Dirk M., Hill, Andrew F., Hochberg, Fred, Horn, Peter A., de Kleijn, Dominique, Kordelas, Lambros, Kramer, Boris W., Krämer‐Albers, Eva‐Maria, Laner‐Plamberger, Sandra, Laitinen, Saara, Leonardi, Tommaso, Lorenowicz, Magdalena J., Lim, Sai Kiang, Lötvall, Jan, Maguire, Casey A., Marcilla, Antonio, Nazarenko, Irina, Ochiya, Takahiro, Patel, Tushar, Pedersen, Shona, Pocsfalvi, Gabriella, Pluchino, Stefano, Quesenberry, Peter, Reischl, Ilona G., Rivera, Francisco J., Sanzenbacher, Ralf, Schallmoser, Katharina, Slaper‐Cortenbach, Ineke, Strunk, Dirk, Tonn, Torsten, Vader, Pieter, van Balkom, Bas W. M., Wauben, Marca, Andaloussi, Samir El, Théry, Clotilde, Rohde, Eva, Giebel, Bernd·2015·Journal of Extracellular Vesicles

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.

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Fig. 1 Pharmaceutical categories and a suggested classification of EV-based therapeutics. Chart depicts the Categories of Medicinal Products with respect to their origin (chemical, biological, herbal). Medicinal Products (according to DIRECTIVE 2001/83/EC) include any substance or combination of substances for treating or preventing disease in humans. Any substance or combination of substances which may be administered to humans with a view to making a medical diagnosis or to restoring, correcting or modifying physiological functions in humans is likewise considered a medicinal product. The suggested classification of EV-based therapeutics within the class of biological medicinal products is provided (grey fields). Bold indicates categories from which existing legislation is recommended to be considered for preclinical and clinical development of EV-therapeutics.
Fig. 1 Pharmaceutical categories and a suggested classification of EV-based therapeutics. Chart depicts the Categories of Medicinal Products with respect to their origin (chemical, biological, herbal). Medicinal Products (according to DIRECTIVE 2001/83/EC) include any substance or combination of substances for treating or preventing disease in humans. Any substance or combination of substances which may be administered to humans with a view to making a medical diagnosis or to restoring, correcting or modifying physiological functions in humans is likewise considered a medicinal product. The suggested classification of EV-based therapeutics within the class of biological medicinal products is provided (grey fields). Bold indicates categories from which existing legislation is recommended to be considered for preclinical and clinical development of EV-therapeutics.CC BY-NC · PubMed Central

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Metadata

Authors
Lener, T., Gimona, M., Aigner, L., Börger, V., Buzas, E., Camussi, G., Chaput, N., Chatterjee, D., Court, F. A., del Portillo, H. A., O'Driscoll, L., Fais, S., Falcon‐Perez, J. M., Felderhoff‐Mueser, U., Fraile, L., Gho, Y. S., Görgens, A., Gupta, R. C., Hendrix, A., Hermann, D. M., Hill, A. F., Hochberg, F., Horn, P. A., de Kleijn, D., Kordelas, L., Kramer, B. W., Krämer‐Albers, E., Laner‐Plamberger, S., Laitinen, S., Leonardi, T., Lorenowicz, M. J., Lim, S. K., Lötvall, J., Maguire, C. A., Marcilla, A., Nazarenko, I., Ochiya, T., Patel, T., Pedersen, S., Pocsfalvi, G., Pluchino, S., Quesenberry, P., Reischl, I. G., Rivera, F. J., Sanzenbacher, R., Schallmoser, K., Slaper‐Cortenbach, I., Strunk, D., Tonn, T., Vader, P., van Balkom, B. W. M., Wauben, M., Andaloussi, S. E., Théry, C., Rohde, E., & Giebel, B.
Affiliations
  • Spinal Cord Injury & Tissue Regeneration Center Salzburg (SCI‐TReCS) Paracelsus Medical University (PMU) Salzburg Austria
  • Institute for Transfusion Medicine University Hospital Essen University of Duisburg‐Essen Essen Germany
  • Department of Genetics, Cell‐ and Immunobiology Semmelweis University Budapest Hungary
  • Molecular Biotechnology Center Department of Medical Sciences University of Turin Turin Italy
  • Laboratory of Immunomonitoring in Oncology UMS 3655 CNRS/US23 Inserm Villejuif France
  • Division of Hematology & Oncology Rhode Island Hospital Providence RI USA
  • Department of Physiology Faculty of Biology Pontificia‐Universidad Católica de Chile Santiago Chile
  • ICREA at Barcelona Centre for International Health Research (CRESIB) Hospital Clínic – Universitat de Barcelona Barcelona Spain
  • School of Pharmacy and Pharmaceutical Sciences Trinity College Dublin Dublin Dublin 2 Ireland
  • Anti‐Tumor Drugs Section Department of Therapeutic Research and Medicines Evaluation National Institute of Health (ISS) Rome Italy
  • Metabolomics Unit CIC bioGUNE CIBERehd Bizkaia Technology Park Derio Spain
  • Department of Paediatrics I Neonatology University Hospital Essen University Duisburg‐Essen Essen Germany
  • Departament de Producció Animal ETSEA Universitat de Lleida Lleida Spain
  • Department of Life Sciences Pohang University of Science and Technology Pohang Republic of Korea
  • Department of Pharmacology and Toxicology University of Louisville Louisville KY USA
  • Laboratory of Experimental Cancer Research Department of Radiation Oncology and Experimental Cancer Research Ghent University Hospital Ghent Belgium
  • Department of Neurology University Hospital Essen University of Duisburg‐Essen Essen Germany
  • Department of Biochemistry and Genetics La Trobe Institute for Molecular Science La Trobe University Melbourne Australia
  • Massachusetts General Hospital Boston MA USA
  • Department of Surgery YLL School of Medicine NUS Singapore Singapore
  • Department of Bone Marrow Transplantation University Hospital Essen University of Duisburg‐Essen Essen Germany
  • Experimental Perinatology/Neonatology School of Mental Health and Neuroscience School of Oncology and Developmental Biology Maastricht University Medical Center Maastricht The Netherlands
  • Molecular Cell Biology and Focus Program Translational Neurosciences University of Mainz Mainz Germany
  • Research and Cell Services Finnish Red Cross Blood Service Helsinki Finland
  • Division of Stem Cell Neurobiology Department of Clinical Neurosciences Wellcome Trust‐Medical Research Council Stem Cell Institute University of Cambridge Cambridge UK
  • Department of Cell Biology Center for Molecular Medicine University Medical Center Utrecht The Netherlands
  • Institute of Medical Biology Agency for Science Technology and Research (A*STAR) Singapore Singapore
  • Krefting Research Centre Institute of Medicine the Sahlgrenska Academy University of Gothenburg Gothenburg Sweden
  • Harvard Medical School Massachusetts General Hospital Boston MA USA
  • Dpto. Biología Celular y Parasitologia Facultat de Farmacia Universitat de Valencia Valencia Spain
  • Institute for Environmental Health Sciences and Hospital Infection Control Medical Center University of Freiburg Freiburg im Breisgau Germany
  • Division of Molecular and Cellular Medicine National Cancer Center Research Institute Tokyo Japan
  • Departments of Transplantation and Cancer Biology Mayo Clinic Jacksonville FL USA
  • Centre for Cardiovascular Research Department of Clinical Biochemistry Aalborg University Hospital Aalborg University Aalborg Denmark
  • Mass Spectrometry and Proteomics Institute of Biosciences and BioResources National Research Council of Italy Naples Italy
  • 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
  • Institute of Molecular Regenerative Medicine Spinal Cord Injury & Tissue Regeneration Center Salzburg (SCI‐TReCS) Paracelsus Medical University (PMU) Salzburg Austria
  • Ralf Sanzenbacher Paul‐Ehrlich‐Institut Bundesinstitut für Impfstoffe und biomedizinische Arzneimittel Federal Institute for Vaccines and Biomedicines Langen Germany
  • Cell Therapy Facility Department of Clinical Pharmacy University Medical Center Utrecht Utrecht The Netherlands
  • Experimental & Clinical Cell Therapy Institute Spinal Cord Injury & Tissue Regeneration Center Salzburg (SCI‐TReCS) Paracelsus Medical University Salzburg Austria
  • Institute for Transfusion Medicine Dresden German Red Cross Blood Donation Service North‐East Dresden Germany
  • Laboratory of Clinical Chemistry and Hematology University Medical Center Utrecht Utrecht The Netherlands
  • Department of Nephrology and Hypertension University Medical Center Utrecht Utrecht The Netherlands
  • Department of Biochemistry and Cell Biology Faculty of Veterinary Medicine Utrecht University Utrecht The Netherlands
  • Department of Physiology, Anatomy and Genetics University of Oxford Oxford UK
  • INSERM U932 Institut Curie Paris France
Venue
Journal of Extracellular Vesicles
Publisher
Wiley
Published
2015-01
Volume
4
Issue
1
ISSN
2001-3078
Cited by
1,491
References
18
Language
en

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Lener, T., Gimona, M., Aigner, L., Börger, V., Buzas, E., Camussi, G., Chaput, N., Chatterjee, D., Court, F. A., del Portillo, H. A., O'Driscoll, L., Fais, S., Falcon‐Perez, J. M., Felderhoff‐Mueser, U., Fraile, L., Gho, Y. S., Görgens, A., Gupta, R. C., Hendrix, A., . . . Giebel, B. (2015). Applying extracellular vesicles based therapeutics in clinical trials – an ISEV position paper. Journal of Extracellular Vesicles. https://doi.org/10.3402/jev.v4.30087