Journal of Clinical Immunology and Allergy

Induction of tolerance for antigen-specific therapy of Graves’ disease and orbitopathy

16^th EuroSciCon Conference on Immunology
March 11-12, 2019 | Amsterdam, Netherlands

Martin Ungerer

AdvanceCOR-GmbH, Germany

Posters & Accepted Abstracts: J Clin Immunol Allergy

DOI: 10.21767/2471-304X-C1-009

Abstract

Graves’ disease is an autoimmune disorder, which is characterized by stimulatory antibodies targeting the human thyrotropin receptor (TSHR), resulting in hyperthyroidism and multiple organ damage. The disease can be modelled in mice using adenoviral immunizations with the extracellular A subunit of the TSHR, which induces a long-term stable disease state. TSHR binding cAMP-stimulatory antibodies, thyroid enlargement, elevated serum thyroxin levels, tachycardia, cardiac hypertrophy and orbitopathy are observed in these Ad-TSHR-immunized mice. T cell epitope-derived linear peptides have been identified using immunized HLA-DR3 transgenic mice, which may induce tolerance towards TSHR at the group of David Wraith, Birmingham, UK. A combination of such peptides have being investigated in a first clinical phase I trial with encouraging results in patients with Graves´ disease at Apitope Inc. Alternatively, cyclic peptides derived from the interaction site of the TSHR A domain with stimulatory anti-TSHR antibodies were injected intravenously in monthly intervals into mice modelling Graves´ disease. These administrations of cyclic peptides were each timed two weeks after the respective Ad-TSHR immunizations, and re-established tolerance towards the antigen, improving symptoms of Graves’ disease within 3 – 4 months after starting these therapies. In immunologically naïve mice, administration of the cyclic peptides did not induce any immune response.

Biography

Medical school at the University of Munich, Germany, and at the Universities of Marseille and Nice, France post-doc in the lab of Prof. Martin Lohse and Prof. Ernst Winnacker, Gene Center, Max-Planck-Institute for Biochemistry, Martinsried, Germany Resident/Senior House Officer at the1st Medical Clinic Rechts der Isar and German Heart Center, TUM University of Munich, training in internal medicine and cardiology Phd promotion ("Habilitation") at TUM University of Munich. Founder and member of the company management of ProCorde GmbH, Corimmun GmbH and advanceCOR GmbH - biotech companies which established novel technologies and drugs for the treatment of thrombosis, cardiac and immunological diseases approved professor of internal medicine and cardiology at the University of Würzburg member of the „Translational Research Group“ steering committee of the German Centre for Cardiovascular Research, Berlin.

E-mail: ungerer@advancecor.com