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Ochsenreither/Letsch Group

Focus of research

  • Identification of new antigens and associated T-cell epitopes for acute myeloid leukemia and ovarian cancer
  • Expression of checkpoint molecules in ovarian cancer
  • Generation of 3D tumor organoids from colorectal carcinoma patients containing autologous immune cells to investigate mechanisms of unspecific immunotherapy
  • CAR-transgenic NK cells for the secretion of cytokines in the tumor microenvironment for combination with checkpoint inhibition

Group Leader

PD Dr. med. Sebastian Ochsenreither

Senior physician, Head of the group

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PD Dr. med. Anne Letsch

Senior physician, Head of the group

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Immunotherapeutic strategies are pivotal for cancer treatment. T-cells form the most important part of the specific immune response against malignant cells. T-cell based therapies have made great progress during the last years. The unspecfic immune therapy by so-called checkpoint inhibition has been established as an important pillar of the tumor therapy. Therapies with T-cells of defined specificities against tumor-associated target proteins have reached clinical practice for the treatment of leukemia and lymphoma.

For checkpoint inhibition antibodies are used to block receptors, by which tumors are able to inactivate potentially otherwise efficient specific T-cell responses. Most important current activities in clinical and pre-clinical research are the development of new target receptors, the combination of different treatment strategies and the identification of predictive markers for response of such therapies.

Targeted T-cell therapy is based on T-cells, which are able to recognize tumor-specific proteins. Currently, research focuses on the production and use of genetic modified T-cells, which gain tumor-specificity by introduction of a second, tumor-specific T-cell receptor. Alternatively, T-cells can become tumor-specific by introduction of a chimeric antigen receptor (CAR), which contains parts of antibodies and receptors. With such CAR, T-cells can be activated by surface proteins like receptors on malignant cells. Until now CAR- based therapies  are mainly used in leukemias and lymphomas, but might also have potential in solid malignancies

Selected publications

  • Schmitt TM, Aggen DH, Ishida-Tsubota K, Ochsenreither S, Kranz DM, Greenberg PD: Generation of higher affinity T cell receptors by antigen-driven differentiation of progenitor T cells in vitro. Nat Biotechnol. 2017
  • Taube ET, Denkert C, Sehouli J, Kunze CA, Dietel M, Braicu I, Letsch A, Darb-Esfahani S: Wilms tumor protein 1 (WT1)-- not only a diagnostic but also a prognostic marker in high-grade serous ovarian carcinoma. Gynecol Oncol. 2016
  • Dielmann A, Letsch A, Nonnenmacher A, Miller K, Keilholz U, Busse A: Favorable prognostic influence of T-box transcription factor Eomesodermin in metastatic renal cell cancer patients. Cancer Immunol Immunother. 2016
  • Busse A, Letsch A, Fusi A, Nonnenmacher A, Stather D, Ochsenreither S, Regenbrecht CR, Keilholz U: Characterization of small spheres derived from various solid tumor cell lines: are they suitable targets for T cells? Clin Exp Metastasis. 2013
  • Chapuis AG, Ragnarsson GB, Nguyen HN, Chaney CN, Pufnock JS, Schmitt TM, Duerkopp N, Roberts IM, Pogosov GL, Ho WY, Ochsenreither S, Wölfl M, Bar M, Radich JP, Yee C, Greenberg PD: Transferred WT1-reactive CD8+ T cells can mediate antileukemic activity and persist in post-transplant patients. Sci Transl Med. 2013
  • Ochsenreither S, Majeti R, Schmitt T, Stirewalt D, Keilholz U, Loeb KR, Wood B, Choi YE, Bleakley M, Warren EH, Hudecek M, Akatsuka Y, Weissman IL, Greenberg PD: Cyclin-A1 represents a new immunogenic targetable antigen expressed in acute myeloid leukemia stem cells with characteristics of a cancer-testis antigen. Blood. 2012
  • Ochsenreither S, Fusi A, Busse A, Bauer S, Scheibenbogen C, Stather D, Thiel E, Keilholz U, Letsch A: "Wilms Tumor Protein 1" (WT1) peptide vaccination-induced complete remission in a patient with acute myeloid leukemia is accompanied by the emergence of a predominant T-cell clone both in blood and bone marrow. J Immunother. 2011

Cooperation partners

  • T. Schmidt, Fred Hutchinson Cancer Research Center, WA Seattle, USA
  • J. Walz, A. Nelde, H. Schuster, University of Tübingen
  • A. Kaufmann, I. Braicu, J. Sehouli, Dpt- of Gynecology, Charité
  • A. Albers, Klinik für Hals-Nasen-Ohrenheilkunde, Charité
  • AG Pezzutto / AG Blankenstein / AG Willimsky, Max Dellbrück Center for Molecular Medicine (MDC)
  • AG Künkele, Dpt. of Pediatric Oncology, Charité

Funding sources

  • Berliner Krebsgesellschaft
  • Sander-Stiftung
  • DKTK - Deutsches Konsortium für Translationale Krebsforschung
  • Deutsche Krebshilfe