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Regeneration

Experimentelle Immuntherapien

Michael Schmück-Henneresse

Wir interessieren uns dafür, wie T-Zellen uns vor viralen Infektionen und chronischen Krankheiten schützen, welche durch Pathogene, Tumore oder Autoimmunität entstehen. Unsere Forschungsarbeiten fokussieren sich auf die Frage, wie T-Zellen eine effektives Immungedächtnis gegen virus-infizierte oder maligne Zellen koordinieren und wie dieses bei Autoimmunkrankheiten oder Transplantationen gezielt abgeschwächt werden kann. Hierzu entwickeln wir Technologien, die die T-Zell-Spezifität detektieren, charakterisieren und genetisch umprogrammieren können sowie Strategien, um die Qualität von T-Zellen für therapeutische Zwecke zu optimieren. Unser Ziel ist es, diagnostische Werkzeuge zur Prädiktion der Immunantwort zu entwickeln, sowie neue Behandlungsoptionen durch die Entwicklung entsprechender T-Zell-Produkte zur Verfügung zu stellen.

  • Gezielte Anpassung eines Homing-Chemokin-Systems für chimäre Antigenrezeptor (CAR)-T-Zellprodukte: CONAN (BMBF-gefördert)
  • T-Zell-Migration und -Aktivierung bei Autoimmunität, Transplantation und Krebsleiden 
  • T-Zell-Gedächtnis /-Differenzierung
  • Entwicklung der nächsten Generation regulatorischer und antigenspezifischer T-Zell-Produkte
  • CRISPR-Cas-vermittelte gezielte Gen-Editierung von T-Zellen 
  • Lösungsansätze für Immunpathologien verursacht durch CRISPR-Cas Gen-Editierungen

Ausgewählte Publikationen
 

  • The Intra-tumoral CXCR3 Chemokine System Is Predictive of Chemotherapy Response in Human Bladder Cancer. Vollmer T, … and Schmueck-Henneresse M, Science Translational Medicine, 2021, Activity of the CXCR3alt-CXCL11 chemokine system in CD8+ stem-like T cells predicts chemotherapy response in patients with bladder cancer.
  • Cas9-directed immune tolerance in humans – A model to evaluate regulatory T cells in gene therapy? Wagner DL, Peter L and Michael Schmueck-Henneresse, Gene Therapy, 2021, Review Article that summarizes the recent evidence on Cas9-specific immunity in humans – including early results from clinical trials, discusses the risks for in vivo gene therapies, and highlight the potential role of Cas9-specific Treg cells to promote immune tolerance.
  • CRISPR-Cas-edited Tacrolimus-resistant antiviral T-cells for advanced adoptive immunotherapy in transplant recipients. Amini L, … and Schmueck-Henneresse M, Molecular Therapy, 2020, Therapeutic antiviral T-cells resistant to immunosuppression
  • High prevalence of S. pyogenes Cas9-reactive T-cells within the adult human population. Wagner DL, … Volk HD and Schmueck-Henneresse M, Nature Medicine, 2019 First report on memory T cell immune responses to CRISPR-associated nucleases
  • Comprehensive characterization of a next-generation antiviral T-cell product and feasibility for application in immunosuppressed transplant patients. Amini L, … and Schmueck-Henneresse M, Frontiers in Immunology, 2019 Characterization and application of a novel protocol for the generation of a superior anti-viral T cell product to organ transplant patients
  • The value of a rapid test of human regulatory T cell function needs to be revised. Wendering DJ, … and Schmueck-Henneresse M, Frontiers in Immunology, 2019 Null-results publication for the correction of a clinically applied assay for testing regulatory T cell function
  • Comprehensive approach for identifying the T-cell subset origin of CD3 and CD28 antibody-activated chimeric antigen receptor-modified T-cells, Schmueck-Henneresse M, ... Rooney CM. J Immunol., 2017Characterization of CAR T cell products and identification of the T cell subset origin within products
  • Comprehensive approach for identifying the T-cell subset origin of CD3 and CD28 antibody-activated chimeric antigen receptor-modified T-cells. Schmueck-Henneresse M, Omer B, Shum T, Tashiro H, Mamonkin M, Lapteva N, Sharma S, Rollins L, Dotti G, Reinke P, Volk HD and Rooney CM. J Immunol., 2017
  • Peripheral Blood-Derived Virus-Specific Memory Stem T Cells Mature to Functional Effector Memory Subsets with Self-Renewal Potency. Schmueck-Henneresse M, Sharaf S, Vogt K, Weist BJ, Landwehr-Kenzel S, Fuehrer H, Jurisch A, Babel N, Rooney CM, Reinke P and Volk HD.  J Immunol., 2015
  • HCMV-specific T-cell therapy: do not forget supply of help.Hammoud B*, Schmueck M*, Fischer AM, Fuehrer H, Akyuez L, Raftery MJ, Schönrich G, Park S-J, Schefold JC, Kaufmann AM, Volk HD, Reinke P. J Immunotherapy, 2013
  •  Preferential expansion of human virus-specific multifunctional central-memory T cells by partial targeting the IL-2 receptor signaling pathway – the key role of CD4+ T cells. Schmueck M, Fischer AM, Hammoud B, Brestrich G, Fuehrer H, Luu SH, Mueller K, Babel N, Volk HD and Reinke P. J Immunol., 2012

Beiträge / Co-Autorenschaft

  • Steiner S, Sotzny F, Bauer S, Na I-K, Schmueck-Henneresse M, Corman VM,   Schwarz T, Drosten C,   Wendering DJ, Behrends U, Volk HD, Scheibenbogen C and Hanitsch LG, HCoV- and SARS-CoV-2 cross-reactive T cells in CVID patients. Frontiers in Immunology, 2020
  • Bajda S, Blazquez-Navarro A, Samans B, Wehler P, Kaliszczyk S, Amini L, Schmueck-Henneresse M, Witzke O, Dittmer U, Westhoff TH, Viebahn R, Reinke P, Thomusch O, Hugo C, Olek S, Roch T, Babel N, The role of soluble mediators in the clinical course of EBV infection and B cell homeostasis after kidney transplantation. Sci. Rep., 2020
  • Roemhild A, Otto NM, Moll G, Abou-El-Enein M, Kaiser D, Bold G, Schachtner T, Choi M, Oellinger R, Landwehr-Kenzel S, Juerchott K, Sawitzki B, Giesler C, Sefrin A, Beier C, Wagner DL, Schlickeiser S, Streitz M, Schmueck-Henneresse M, Amini L, Stervbo U, Babel N, Volk HD, Reinke P, Regulatory T cells for minimising immune suppression in kidney transplantation: phase I/IIa clinical trial.BMJ, 2020
  • Boucault L,  Lopez Robles MD,  Thiolat A,  Bézie S,  Schmueck-Henneresse M,  Braudeau C,  Vimond N, Freuchet A,  Autrusseau E,  Charlotte F,  Redjoul R,  Beckerich F,  Leclerc M,  Piaggio E,  Josien R, Volk HD,  Maury S,  Cohen JL,  Anegon I,  Guillonneau C, Transient Antibody Targeting of CD45RC Inhibits the Development of Graft-versus-Host Disease. Blood Advances, 2020
  • Thieme CJ, Weist BJD, Mueskes A, Roch T, Stervbo U, Rosiewicz K, Wehler P, Stein M, Nickel P, Kurtz A, Lachmann N, Choi M, Schmueck-Henneresse M, Westhoff TH, Reinke P, Babel N, The TreaT-Assay: A Novel Urine-Derived Donor Kidney Cell-Based Assay for Prediction of Kidney Transplantation Outcome. Sci. Rep., 2019
  • Omer B, Castillo PA, Tashiro H, Shum T, Huynh MTA, Cardenas M, Tanaka M, Lewis A, Sauer T, Parihar R, Lapteva N, Schmueck-Henneresse M, Mukherjee M, Gottschalk S and Rooney CM, Chimeric Antigen Receptor Signaling Domains Differentially Regulate Proliferation and Native T Cell Receptor Function in Virus-Specific T Cells. Frontiers in Medicine, 2018
  • Landwehr-Kenzel S, Zobel A, Hoffmann H, Landwehr N, Schmueck-Henneresse M, Schachtner T, Roemhild A and Reinke P. Ex vivo expanded natural regulatory T cells from patients with end-stage renal disease or kidney transplantation are useful for autologous cell therapy. Kidney Int., 2018
  • Weist BJ, Wehler P, El Ahmad L, Schmueck-Henneresse M, Millward JM, Nienen M, Neumann AU, Reinke P, Babel N. A revised strategy for monitoring BKV-specific cellular immunity in kidney transplant patients. Kidney Int., 2015
  • Weist BJ, Schmueck M, Fuehrer H, Sattler A, Reinke P, Babel N. The role of CD4+ T cells in BKV-specific T cell immunity. Med Microbiol Immunol., 2014
  • Landwehr-Kenzel S, Issa F, Luu SH, Schmueck M, Lei H, Zobel A, Thiel A, Babel N, Wood K, Volk HD, Reinke P. Novel GMP-Compatible Protocol Employing an Allogeneic B Cell Bank for Clonal Expansion of Allospecific Natural Regulatory T Cells.Am J Transplant., 2014
  • Hashimdeen SS, Römhild A, Schmueck M, Kratz K, Lendlein A, Kurtz A, Reinke P. Culture surface influence on T-cell phenotype and function.Clin Hemorheol Microcirc., 2013
  • Schwele S, Fischer AM, Brestrich G, Wlodarski MW, Wagner L, Schmueck M, Roemhild A, Thomas S, Hammer MH, Babel N, Kurtz A, Maciejewski JP, Reinke P, Volk HD. Cytomegalovirus-Specific Regulatory and Effector T Cells Share TCR Clonality-Possible Relation to Repetitive CMV Infections. Am J Transplant., 2012
  • Brestrich G, Zwinger S, Fischer A, Schmueck M, Röhmhild A, Hammer MH, Kurtz A, Uharek L, Knosalla C, Lehmkuhl H, Volk HD, Reinke P. Adoptive T-Cell Therapy of a Lung Transplanted Patient with Severe CMV Disease and Resistance to Antiviral Therapy.Am J Transplant., 2009