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Immunology 2018
J u l y 0 5 - 0 7 , 2 0 1 8
V i e n n a , A u s t r i a
Page 85
Journal of Clinical Immunology and Allergy
ISSN 2471-304X
1 5
t h
I n t e r n a t i o n a l C o n f e r e n c e o n
Immunology
G
raves’ 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.
Induction of tolerance for antigen-specific therapy of
Graves´ disease and orbitopathy
Martin Ungerer
AdvanceCOR-GmbH, Germany
Martin Ungerer, Insights Allergy Asthma Bronchitis 2018, Volume: 4
DOI: 10.21767/2471-304X-C1-003
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,
CorimmunGmbHand advanceCORGmbH- 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.
ungerer@advancecor.com