SFB 1192
Project B5
Nanobody-based treatment strategies in glomerulonephritis
While several glomerular diseases such as membranous nephropathy and anti-GBM disease are caused by autoantibodies, antigen-specific therapies are still missing. However, the involved autoantigens represent promising targets for treatments aiming at the underlying disease pathomechanisms while not affecting protective immunity. In the last funding period, we successfully generated antigen-specific autoimmune mouse models as well as therapeutic antibodies targeting pathogenic plasma cells. Based on this work, we now aim to develop and evaluate strategies to treat antibody-mediated diseases of the kidney – particularly membranous nephropathy and anti-GBM disease – on multiple new levels: 1.) Blocking of autoantibody binding to kidney autoantigens using target-specific nanobodies generated e.g. in a llama IgH transgenic mouse line. 2.) Engineering of heavy chain antibodies containing antigen extracellular domains for the specific elimination of antigen-specific autoantibodies (through Fc-receptor-mediated uptake and degradation of immune complexes) and autoantibody-producing B cells (through their specific B cell receptors). 3.) Gene delivery and knockdown using adeno-associated viral vectors (AAVs) displaying nanobodies against cell-specific surface molecules to control local disease processes. In summary, these studies will pave the way for novel antigen-specific treatments for glomerulonephritis, which may also be applicable to other inflammatory and autoantibody-mediated diseases.
Publications
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Molecular consequences of SARS-CoV-2 liver tropism
Wanner N, Andrieux G, Badia-I-Mompel P, Edler C, Pfefferle S, Lindenmeyer MT, Schmidt-Lauber C, Czogalla J, Wong MN, Okabayashi Y, Braun F, Lütgehetmann M, Meister E, Lu S, Noriega MLM, Günther T, Grundhoff A, Fischer N, Bräuninger H, Lindner D, Westermann D, Haas F, Roedl K, Kluge S, Addo MM, Huber S, Lohse AW, Reiser J, Ondruschka B, Sperhake JP, Saez-Rodriguez J, Boerries M, Hayek SS, Aepfelbacher M, Scaturro P, Puelles VG, Huber TB. Nat Metab. 2022 Mar
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Purine Release, Metabolism, and Signaling in the Inflammatory Response.
Linden J, Koch-Nolte F, Dahl G.Annu Rev Immunol. 2019 Jan
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T RM maintenance is regulated by tissue damage via P2RX7.
Stark R, Wesselink TH, Behr FM, Kragten NAM, Arens R, Koch-Nolte F, van Gisbergen KPJM, van Lier RAW.Sci Immunol. 2018 Dec
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CD38-Specific Biparatopic Heavy Chain Antibodies Display Potent Complement-Dependent Cytotoxicity Against Multiple Myeloma Cells.
Schütze K, Petry K, Hambach J, Schuster N, Fumey W, Schriewer L, Röckendorf J, Menzel S, Albrecht B, Haag F, Stortelers C, Bannas P, Koch-Nolte F.Front Immunol. 2018 Nov
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Monitoring the Sensitivity of T Cell Populations Towards NAD+ Released During Cell Preparation.
Rissiek B, Lukowiak M, Haag F, Magnus T, Koch-Nolte F.Methods Mol Biol. 2018 Aug
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Modulating ion channel function with antibodies and nanobodies.
Stortelers C, Pinto-Espinoza C, Van Hoorick D, Koch-Nolte F.Curr Opin Immunol. 2018 Jun
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Nanobody-Based Biologics for Modulating Purinergic Signaling in Inflammation and Immunity.
Menzel S, Schwarz N, Haag F, Koch-Nolte F.Front Pharmacol. 2018 Mar
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Nanobodies that block gating of the P2X7 ion channel ameliorate inflammation.
Danquah W, Meyer-Schwesinger C, Rissiek B, Pinto C, Serracant-Prat A, Amadi M, Iacenda D, Knop JH, Hammel A, Bergmann P, Schwarz N, Assunção J, Rotthier W, Haag F, Tolosa E, Bannas P, Boué-Grabot E, Magnus T, Laeremans T, Stortelers C, Koch-Nolte FSci Transl Med. 2016 Nov
Project-Team
Project Leader
PD. Dr. med. Nicola M. Tomas
Dr. Nicola Wanner
Co-Workers
Marten Junge
Fabienne Seyfried
Gudrun Dubberke