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Research focus of the T cell immunotherapy Lab

Dr. med. Simone Thomas & Prof. Dr. med. Wolfgang Herr

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Contact:

Dr. Simone Thomas

Department of Internal Medicine III

University Hospital Regensburg                                                    Franz-Josef-Strauß-Allee 11                                                         93053 Regensburg                                                                    Phone: +49-941 944-5142   Fax: 0941 944-5143                          e-mail: simone.thomas@ukr.de

www.ukr.de | www.rcii.de


Group members

 

  • Maximilian Schmid (Dr. rer. physiol.)

        Phone: +49-941-944-4845                                                            E-Mail: Maximilian1.Schmid@ukr.de  

  • Sebastian Klobuch (Dr. med.)
       Phone: +49-941-944-5504                                                          E-Mail: Sebastian.Klobuch@ukr.de
  • Carina Mirbeth (BTA)
        Phone: +49-941-944-4846                                                           E-Mail: Carina.Mirbeth@ukr.de
  •  Mareile Siebörger (MTA)
           Phone: +49-941-944-4846                                                            E-Mail: Mareile.Sieboerger@ukr.de
  • Sarah Vatter (M. Sc.)

    Phone:+49-941-944-4845                                                   
    E-Mail: Sarah.Vatter@ukr.de
      
  • Kathrin Hammon (M.Sc. Biochem.)

    Phone: +49-941-944-4845                                                           
    E-Mail: Kathrin.Hammon@ukr.de 
     
  •  Tim Steinberg (cand. med.)

E-Mail: Tim.Steinberg@ukr.de

  • Michael Zwerger (cand. med.)

E-Mail: Michael.Zwerger@ukr.de


 


 Our working group is focusing on the development of cellular immunotherapies in the context of allogenic stem cell transplantation. Our key aspect is the generation of leukemia-specific T cells by stimulating T lymphocytes of healthy donors with defined leukemia antigens. In order to simplify this stimulation process, we focus on the isolation of T cell receptors (TCR) from leukemia-specific T cell clones and the transfer of these TCR via several gene transfer methods (electroporation, retroviral transduction) into T cells from healthy donors. This procedure enables the T cells to detect and eliminate leukemic cells in an antigen-specific manner (see Fig.). Another focus of our group is the development of TCR-based immunotherapies against viral infections.

 

Current Projects:

The effects of IDH mutations on the interplay between metabolism and anti-leukemic immune response             Involved members: Kathrin Hammon, Sebastian Klobuch           Funding: Deutsche Forschungsgemeinschaft (KFO262)

Allogenic lymphocyte therapy: HLA-DP specific T cell receptors for adoptive immunotherapies against leukemias Involved members: Sarah Vatter, Michael Zwerger, Carina Mirbeth Funding: Regensburg Center for Interventional Immunology (RCI), Wilhelm-Sander Stiftung

Allogenic lymphocyte therapy: Development of bispecific soluble TCR molecules for CMV therapy                         Involved members: Maximilian Schmid, Mareile Siebörger     Funding: Regensburg Center for Interventional Immunology (RCI)

Immunologic investigations about biomodulatory therapies of acute myeloid leukemias                                           Involved members: Sebastian Klobuch, Tim Steinberg

 

Selected publications:

2016

Herr W, Eichinger Y, Beshay J, Bloetz A, Vatter S, Mirbeth C, Distler E, Hartwig UF, Thomas S. HLA-DPB1 mismatch alleles represent powerful leukemia rejection antigens in CD4 T-cell immunotherapy after allogeneic stem-cell transplantation. Leukemia 2016 Sep 2. doi: 10.1038/leu.2016.210 [Epub ahead of print]

Knies D, Klobuch S, Xue SA, Birtel M, Echchannaoui H, Yildiz O, Omokoko T, Guillaume P, Romero P, Stauss H, Sahin U, Herr W, Theobald M*, Thomas S*, Voss RH*. An optimized single chain TCR scaffold relying on the assembly with the native CD3-complex prevents residual mispairing with endogenous TCRs in human T-cells. Oncotarget 2016; 7:21199  *shared senior authorship

Distler E, Albrecht J, Brunk A, Khan S, Schnürer E, Frey M, Mottok A, Jordán-Garrote AL, Brede C, Beilhack A, Mades A, Tomsitz D, Theobald M, Herr W*, Hartwig UF*. Patient-individualized CD8+ cytolytic T-cell therapy effectively combats minimal residual leukemia in immunodeficient mice. Int J Cancer. 2016; 138:1256.

2015

Thomas S, Klobuch S, Podlech J, Plachter B, Hoffmann P, Renzaho A, Theobald M, Reddehase MJ*, Herr W*, Lemmermann NA*. Evaluating Human T-Cell Therapy of Cytomegalovirus Organ Disease in HLA-Transgenic Mice. PLoS Pathogen. 2015; 11:e1005049.  *shared last authorship

Zupke O, Distler E, Jürchott A, Paiphansiri U, Dass M, Thomas S, Hartwig U, Theobald M, Landfester K, Mailänder V, Herr W. Nanoparticles and antigen-specific T Cell Therapeutics: a Comprehensive Study on Uptake and Release. Nanomedicine 2015; 10:1063.

Thomas S, Schelker R, Klobuch S, Zaiss S, Troppmann M, Rehli M, Haferlach T, Herr W, Reichle A. Biomodulatory therapy induces complete molecular remission in chemorefractory acute myeloid leukemia. Haematologica 2015; 100:e4

2014

Thomas S, Klobuch S, Sommer M, van Ewijk R, Theobald M, Meyer RG, Herr W. Human CD8+ memory and EBV-specific T cells show low alloreactivity in vitro as well as in CD34+ stem-cell engrafted NOD/SCID/IL-2Rgcnull mice. Exp. Hematol. 2014; 42:28.

Teschner D, Distler E, Wehler D, Frey M, Marandiuc D, Langeveld K, Theobald M, Thomas S, Herr W. Depletion of naive T cells using clinical grade magnetic CD45RA beads: a new approach for GvHD prophylaxis. Bone Marrow Transplant. 2014; 49:138

2013

Sauer C*, Klobuch S*, Herr W, Thomas S**, Plachter B**. Subviral dense bodies of human cytomegalovirus stimulate maturation and activation of monocyte-derived immature dendritic cells. J Virol. 2013; 87: 11287-11291. *shared first authorship; **shared last authorship

2012

Thomas S, Klobuch S, Besold K, Plachter B, Dörrie J, Schaft N, Theobald M, Herr W. Strong and sustained effector function of memory- versus naive-derived T cells upon T-cell receptor RNA tranfer: Implications for cellular therapy. Eur. J. Immunol. 2012; 42:3442

Kleemann P, Distler E, Wagner EM, Thomas S, Klobuch S, Aue S, Schnürer E, Schild H, Theobald M, Plachter B, Tenzer S, Meyer RG, Herr W. Varicella-zoster virus glycoproteins B and E are major targets of CD4+ and CD8+ T cells reconstituting during zoster after allogeneic transplantation. Haematologica 2012; 97:874.

2011

Thomas S, Herr W. Natural and adoptive T-cell immunity against herpes family viruses after allogeneic hematopoietic stem cell transplantation. Immunotherapy. 2011; 3:771

Distler E, Bloetz A, Albrecht J, Asdufan S, Hohberger A, Frey M, Schnürer E, Thomas S, Theobald M, Hartwig UF, Herr W. Alloreactive and leukemia-reactive T cells are preferentially derived from naive precursors in healthy donors: implications for immunotherapy with memory T cells. Haematologica 2011; 96:1024.

2010

Voss RH*, Thomas S*, Pfirschke C, Hauptrock B, Kuball J, Grabowski M, Engel R, Guillaume P, Romero P, Huber C, Beckhove P, Theobald M. Coexpression of the T cell receptor constant alpha domain triggers tumor reactivity of single chain TCR transduced human T cells. Blood. 2010; 115:5154. *shared first authorship.

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