title: Redefining Strategies to Introduce Tolerance-Inducing Cellular Therapy in Human beings to Combat Autoimmunity and Transplantation Reactions.
abstract: Clinical translation of tolerance-inducing cell therapies requires a novel approach focused on innovative networks, patient involvement, and, foremost, a fundamental paradigm shift in thinking from both Academia, and Industry and Regulatory Agencies. Tolerance-inducing cell products differ essentially from conventional drugs. They are personalized and target interactive immunological networks to shift the balance toward tolerance. The human cell products are often absent or fundamentally different in animals. This creates important limitations of pre-clinical animal testing for safety and efficacy of these products and calls for novel translational approaches, which require the combined efforts of the different parties involved. Dedicated international and multidisciplinary consortia that focus on clinical translation are of utmost importance. They can help in informing and educating regulatory policy makers on the unique requirements for these cell products, ranging from pre-clinical studies in animals to in vitro human studies. In addition, they can promote reliable immunomonitoring tools. The development of tolerance-inducing cell products requires not only bench-to-bedside but also reverse translation, from bedside back to the bench.
authors.affiliation: Department of Immunopathology, Division Research and Landsteiner Laboratory, Sanquin Blood Supply, Academic Medical Center, University of Amsterdam , Amsterdam , Netherlands.
authors.forename: Anja
authors.initials: A
authors.lastname: Ten Brinke
authors.affiliation: Laboratory for Medical Immunology, Department of Laboratory Medicine, Radboud University Medical Center , Nijmegen , Netherlands.
authors.forename: Irma
authors.initials: I
authors.lastname: Joosten
authors.affiliation: Department of Immunopathology, Division Research and Landsteiner Laboratory, Sanquin Blood Supply, Academic Medical Center, University of Amsterdam , Amsterdam , Netherlands.
authors.forename: S Marieke
authors.initials: SM
authors.lastname: van Ham
authors.affiliation: Department of Nephrology, Leiden University Medical Center , Leiden , Netherlands.
authors.forename: Cees
authors.initials: C
authors.lastname: van Kooten
authors.affiliation: Laboratory for Translational Immunology, Center for Molecular and Cellular Immunology, Wilhelmina Children's Hospital, University Medical Centre Utrecht , Utrecht , Netherlands.
authors.forename: Berent Jan
authors.initials: BJ
authors.lastname: Prakken
keywords: autoimmunity; dendritic cells; regulatory T cells; regulatory agencies; tolerance; transplantation