Home | Research | Research Groups | T-Cell Therapy T-Cell Therapy Research The T-Cell Therapy Research Group focuses on cellular therapy of hematologic and solid malignancies using CAR/TCR-engineered T cells, and is moving to translate this technology to early-phase clinical trials. In this context, we aim to improve the selectivity and safety of CAR T cells, and to increase CAR T-cell antitumor efficacy by adding cytokine signals to the T cells and by blocking CD30-mediated repression. Currently, we are designing a set of CARs that deliver T-cell activation by combinatorial signaling (combinatorial/split-CAR concept) in order to improve selectivity in leukemia targeting after allogeneic hematopoietic stem cell transplantation. To achieve this we are focusing on allogeneic HLA-DP rejection antigens. In order to protect healthy non-hematopoietic tissues, the CAR will be designed to activate T cells only upon the binding of two antigens co-expressed on the same target cell, and will remain silent when recognizing healthy cells with only one antigen. CAR T cells attacking a cancer cell. T cells (green) engineered with a CAR are recognizing the tumor target antigen and form a synapse (magenta) with the cancer cell (grey). Deeper investigation We are currently working on a number of initiatives in collaboration with other groups and facilities at the Leibniz Institute: We aim to redirect CAR T cells against antigen-loss leukemia/lymphoma cells by employing IL-12-redirected stimulation of CD19 CAR T cells. We do this by inserting the IL-12 protein sequence into the extracellular moiety of the CD19 CAR that polarizes T cells towards NK-like activities. A tumor model will demonstrate the efficacy of IL-12 CAR T cells and their applicability in the treatment of other hematologic and solid tumors with frequent antigen loss. This project is a collaboration with Professor Hinrich Abken. Novel first-in-class CAR constructs that trigger a more efficacious T-cell antitumor response have recently been developed at the LIT. One of these CAR constructs is being translated into a phase-I clinical trial, funded by the German Cancer Aid. This trial aims to apply dual-specific CD30/CEA CAR T cells to liver metastases of CEA+ gastrointestinal cancer. In preclinical models CD30/CEA CAR T cells—developed by Professor Abken’s group—showed prolonged T-cell activation upon CD30 blockade on CAR T cells. In order to fulfill regulatory and safety requirements with respect to Advanced Therapy Medicinal Products (ATMPs), the T-Cell Therapy Group and Professor Hinrich Abken’s group are developing the necessary procedures and applying them to the respective cell product. This is done in close cooperation with the manufacturing laboratory (JCC) and the Core Facility ‘Good Clinical Practice & Regulatory Affairs’ (GCP). More generally, we are establishing prerequisites at the interface between the research laboratory and clinical exploration in order to transfer novel CAR T-cell therapies into clinical trials. In the context of CD30-driven CAR T-cell improvement, we are also developing CD30/CD19 CAR T cells for the treatment of B-cell malignancies. The project also aims to understand the functional benefit of CD30 blockade in activating CAR T cells. In close cooperation with Professor Abken’s group, protein-structure modeling will guide us to improve the CAR structure itself, with the aim of optimizing synapse formation in favor of more durable T-cell activation. Publications Visit the complete list of our Research Group`s publications on Google Scholar: https://scholar.google.de/citations?user=4pOfe-sAAAAJ&hl=de Here is a selection of the most important publications from the last few years: Hammon K, Renner K, Althammer M, Voll F, Babl N, Decking SM, Siska PJ, Matos C, Conejo ZEC, Mendes K, Einwag F, Siegmund H, Iberl S, Berger RS, Dettmer K, Schoenmehl R, Brochhausen C, Herr W, Oefner PJ, Rehli M, Thomas S*, Kreutz M*. D-2-hydroxyglutarate supports a tolerogenic phenotype with lowered major histocompatibility class II expression in non-malignant dendritic cells and acute myeloid leukemia cells. Haematologica. 2024 Jan 18. doi: 10.3324/haematol.2023.283597. PMID: 38235501. Online ahead of print. *shared authorship Heudobler D, Luke F, Hahn J, Grube M, Schlosser P, Kremers S, Sudhoff T, Westermann J, Hutter-Kronke ML, Schlenk RF, Weber D, Paschka P, Zeman F, Dohner H, Herr W, Reichle A*, Thomas S*. Low-dose azacitidine, pioglitazone and all-trans retinoic acid is safe in patients aged ≥ 60 years with acute myeloid leukemia refractory to standard induction chemotherapy (AMLSG 26-16/AML-ViVA): results of the safety run-in phase. Haematologica 2024; 109(4):1274. doi: 10.3324/haematol.2023.283864. PMID: 37881883. *shared authorship Bethge WA, Martus P, Schmitt M, Holtick U, Subklewe M, von Tresckow B, Ayuk F, Wagner-Drouet EM, Wulf GG, Marks R, Penack O, Schnetzke U, Koenecke C, von Bonin M, Stelljes M, Glass B, Baldus CD, Vucinic V, Mougiakakos D, Topp MS, Fante MA, Schroers R, Bayir LM, Borchmann P, Buecklein V, Hanoun C, Thomas S, Beelen DW, Lengerke C, Kroeger N, Dreger P. GLA/DRST real-world outcome analysis of CAR-T cell therapies for large B-cell lymphoma in Germany. Blood 2022; 140(4):349. doi: 10.1182/blood.2021015209. PMID: 35316325 Jetani H, Navarro-Bailón A, Maucher M, Frenz S, Verbruggen C, Yeguas A, Vidriales MB, González M, Saborido JR, Kraus S, Mestermann K, Thomas S, Bonig H, Luu M, Monjezi R, Mougiakakos D, Sauer M, Einsele H, Hudecek M. Siglec-6 is a novel target for CAR T-cell therapy in acute myeloid leukemia (AML). Blood 2021; 138(19):1830. doi: 10.1182/blood.2020009192. PMID: 34289026 Klobuch S, Hammon K, Vatter-Leising S, Neidlinger E, Zwerger M, Wandel A, Neuber LM, Heilmeier B, Fichtner R, Mirbeth C, Herr W, Thomas S. HLA-DPB1 Reactive T Cell Receptors for Adoptive Immunotherapy in Allogeneic Stem Cell Transplantation. Cells 2020; 9(5):1264. doi: 10.3390/cells9051264. PMID: 32443793 Jetani H, García Cadenas I, Nerreter T, Thomas S, Rydzek J, Briones Meijide J, Bonig H, Herr W, Sierra J, Einsele H, Hudecek M. CAR T-cells targeting FLT3 have potent activity against FLT3-ITD+ AML and act synergistically with the FLT3-inhibitor crenolanib. Leukemia 2018; 32(5):1168. doi: 10.1038/s41375-018-0009-0. PMID: 29472720 Mathew NR, Baumgartner F, Braun L, O’Sullivan D, Thomas S, Waterhouse M, Müller TA, Hanke K, Taromi S, Apostolova P, Illert AL, Melchinger W, Duquesne S, Schmitt-Graeff A, Osswald L, Yan KL, Weber A, Tugues S, Spath S, Pfeifer D, Follo M, Claus R, Lübbert M, Rummelt C, Bertz H, Wäsch R, Haag J, Schmidts A, Schultheiss M, Bettinger D, Thimme R, Ullrich E, Tanriver Y, Vuong GL, Arnold R, Hemmati P, Wolf D, Ditschkowski M, Jilg C, Wilhelm K, Leiber C, Gerull S, Halter J, Lengerke C, Pabst T, Schroeder T, Kobbe G, Rösler W, Doostkam S, Meckel S, Stabla K, Metzelder SK, Halbach S, Brummer T, Hu Z, Dengjel J, Hackanson B, Schmid C, Holtick U, Scheid C, Spyridonidis A, Stölzel F, Ordemann R, Müller LP, Sicre-de-Fontbrune F, Ihorst G, Kuball J, Ehlert JE, Feger D, Wagner EM, Cahn JY, Schnell J, Kuchenbauer F, Bunjes D, Chakraverty R, Richardson S, Gill S, Kröger N, Ayuk F, Vago L, Ciceri F, Müller AM, Kondo T, Teshima T, Klaeger S, Kuster B, Kim DDH, Weisdorf D, van der Velden W, Dörfel D, Bethge W, Hilgendorf I, Hochhaus A, Andrieux G, Börries M, Busch H, Magenau J, Reddy P, Labopin M, Antin JH, Henden AS, Hill GR, Kennedy GA, Bar M, Sarma A, McLornan D, Mufti G, Oran B, Rezvani K, Shah O, Negrin RS, Nagler A, Prinz M, Burchert A, Neubauer A, Beelen D, Mackensen A, von Bubnoff N, Herr W, Becher B, Socié G, Caligiuri MA, Ruggiero E, Bonini C, Häcker G, Duyster J, Finke J, Pearce E, Blazar BR, Zeiser R. Sorafenib promotes graft-versus-leukemia activity in mice and humans through IL-15 production in FLT3-ITD-mutant leukemia cells. Nat Med 2018; 24(3):282. doi: 10.1038/nm.4484. PMID: 29431743 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 2017; 31(2):434. doi: 10.1038/leu.2016.210. PMID: 27479183 Thomas S, Klobuch S, Podlech J, Plachter B, Hoffmann P, Renzaho A, Theobald M, Reddehase M, Herr W, Lemmermann N. Evaluating human T-cell therapy of cytomegalovirus organ disease in HLA-transgenic mice. PLoS Pathog 2015; 11(7):e1005049. doi: 10.1371/journal.ppat.1005049. PMID: 26181057 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 and in CD34+ stem cell-engrafted NOD/SCID/IL-2Rγc null mice. Exp Hematol 2014; 42(1):28. doi: 10.1016/j.exphem.2013.09.013. PMID: 24120693 Thomas S, Klobuch S, Besold K, Plachter B, Dörrie J, Schaft N, Theobald M, Herr W. Strong and sustained effector function of memory- versus naïve-derived T cells upon T-cell receptor RNA transfer: implications for cellular therapy. Eur J Immunol 2012; 42(12):3442. doi: 10.1002/eji.201242666. PMID: 22930221 Voss RH*, Thomas S*, Pfirschke C, Hauptrock B, Klobuch S, 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(25):5154. doi: 10.1182/blood-2009-11-254078. PMID: 20378753. *shared authorship Translation Our T-Cell Therapy Research Group focus on the development of novel T-cell immunotherapies for the treatment of patients with hematologic and solid malignancies. Currently, we are establishing a clinical phase-I trial that explores a novel next-generation CAR design for the treatment of patients with metastatic colorectal cancer. Funding We would like to thank the funding agencies who support our work: Wilhelm-Sander Foundation ‘Improving CAR T-cell efficacy against leukemia/lymphoma with antigen loss by a novel CAR design that provides CAR T cells with NK-like capabilities.’ Website WSSt German Research Foundation (DFG) ‘Efficacy and safety of HLA-DPB1-specific T-cell receptors as mediators of graft-versus-leukemia effect (TP A02 SFB/TR221).’ Website DFG German cancer aid ‘Phase-I trial on safety, dose, and feasibility of RCI-CART-CEA/30 in patients with CEA positive liver metastases from colorectal cancer.’ Website DKH Team & Lab Life Prof. Simone Thomas Head of Research Group | T-Cell Therapy Tel: +49 941 944–5142 Email: simone.thomas@ukr.de Research team Prof. Simone Thomas Head of Research Group | T-Cell Therapy Helena Janning PhD Student Patrick Elsenbroich MD Student Charlotte Schenkel Research Technician Previous Next Close Helena Janning PhD Student T Cell Therapy Tel: +49 941 944-38117 Email: Helena.Janning@ukr.de Close Patrick Elsenbroich MD Student Genetic Immunotherapy + T-Cell Therapy Tel: +49 941 944- Email: Patrick.Elsenbroich@stud.uni-regensburg.de Close Charlotte Schenkel Research Technician T-Cell Therapy Tel: +49 941 944-38117 Email: charlotte.schenkel@ukr.de Lab Life There is life outside the laboratory: The Leibniz Institute places great value on our scientists developing the team spirit both in and out of work. 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