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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.

Selected Publications:

  • ATP-Gated P2X7-Ion Channel on Kidney-Resident Natural Killer T Cells and Memory T Cells in Intrarenal Inflammation.

    Marten Junge, Nastassia Liaukouskaya, Nicole Schwarz, Carolina Pinto-Espinoza, Alessa Z Schaffrath, Björn Rissiek, Christian F Krebs, Guido Rattay, Hans-Willi Mittrücker, Nicola M Tomas, Annette Nicke, Friedrich Haag, Tobias B Huber, Catherine Meyer-Schwesinger, Friedrich Koch-Nolte, Nicola Wanner.  JASN. 2025 Apr

  • Passive transfer of patient-derived anti-nephrin autoantibodies causes a podocytopathy with minimal change lesions.

    Felicitas E. Hengel, Silke Dehde, Oliver Kretz, Jonas Engesser, Tom Zimmermann, Tobias B. Huber, Nicola M. Tomas.  J Clin Invest. 2025 Jan

  • Autoantibodies Targeting Nephrin in Podocytopathies.

    Hengel FE, Dehde S, Lassé M, Zahner G, Seifert L, Schnarre A, Kretz O, Demir F, Pinnschmidt HO, Grahammer F, Lucas R, Mehner LM, Zimmermann T, Billing AM, Oh J, Mitrotti A, Pontrelli P, Debiec H, Dossier C, Colucci M, Emma F, Smoyer WE, Weins A, Schaefer F, Alachkar N, Diemert A, Hogan J, Hoxha E, Wiech T, Rinschen MM, Ronco P, Vivarelli M, Gesualdo L, Tomas NM, Huber TB. N Engl J Med. 2024 Aug

  • The classical pathway triggers pathogenic complement activation in membranous nephropathy.

    Larissa Seifert, Gunther Zahner, Catherine Meyer-Schwesinger, Naemi Hickstein, Silke Dehde, Sonia Wulf, Sarah M S Köllner, Renke Lucas, Dominik Kylies, Sarah Froembling, Stephanie Zielinski, Oliver Kretz, Anna Borodovsky, Sergey Biniaminov, Yanyan Wang, Hong Cheng, Friedrich Koch-Nolte, Peter F Zipfel, Helmut Hopfer, Victor G Puelles, Ulf Panzer, Tobias B Huber, Thorsten Wiech, Nicola M Tomas. Nat Commun. 2023 Jan

  • 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

Project-Team

Project Leader
PD. Dr. med. Nicola M. Tomas
Dr. Nicola Wanner