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Clinical Therapeutic Tolerance: First-in-Human Data: Proceedings of the 4th Newcastle Therapeutic Tolerance Workshop

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The concept of therapeutic tolerance in animal models of immunopathology is not new. Researchers have been tolerising to allografts, and to autoantigens, using a variety of approaches for 30 years. However, translation to the clinic has been slow. Potential reasons include genetic polymorphism, ...

The concept of therapeutic tolerance in animal models of immunopathology is not new. Researchers have been tolerising to allografts, and to autoantigens, using a variety of approaches for 30 years. However, translation to the clinic has been slow. Potential reasons include genetic polymorphism, environmental factors such as allergens and infections in humans, and late presentation of clinical autoimmune diseases. A major hurdle is poor understanding of immune dysregulation underpinning many human autoimmune conditions, and the paucity of reliable biomarkers of tolerance. However, the tide is finally turning. We now have much better understanding of pre-autoimmune states in some conditions – notably type 1 diabetes and rheumatoid arthritis. Furthermore, the underlying immune dysregulation is slowly being addressed, both with hypothesis driven research and comprehensive systems analyses . Experimental medicine approaches are also helping to identify biomarkers of tolerance induction and breakdown in human transplantation and cancer immunotherapy, respectively. Additionally novel approaches, such as cellular therapies, are being tested in the clinic, and the ethical landscape is permitting intervention at earlier stages of autoimmunity, when reinforcing tolerance may be more tractable.

Over the past 12 years we have held regular workshops in Newcastle upon Tyne, with a focus on clinical therapeutic tolerance. The titles of these workshops reflect the changing landscape. The first, in June 2005 was entitled ‘Therapeutic Tolerance: Myth or Reality?’ In 2009 we entitled our workshop ‘Therapeutic Tolerance: Closer to Reality?’ and, in 2013, ‘Tolerance Inducing Strategies in the Clinic’. Our fourth workshop is entitled ‘Therapeutic Tolerance: First results’. For the first time we will have talks focussed on breaking tolerance in cancer, to complement our more traditional focus on therapeutic tolerance induction. This collection of articles is written by Faculty from our 2017 workshop and provides a state-of-the-art review of the tolerance field.


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