Pediatric Hematology, Oncology, and Hemostaseology -
Dr. Ulrike Köhl

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Expertise

• Focus of interest is the development and timing of cellular immunotherapies in childhood malignant disease. These include the generation and optimization of suicide gene transduced T cells for secure donor lymphocyte infusions after allogeneic hematopoetic stem cell transplantation. In a binational phase I trial, patients with malignant diseases are treated with highly enriched and expanded NK cells.
  
• A second line of interest focuses on the interaction of NK cells with other immune cells in the context of cytotoxic reactions. Of special interest are the cellular mechanisms that lead to enhanced cytotoxicity.
  
  

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Resources and Abilities

• Research scale, clinical scale and clinical grade cell selection of stem cells, T cells, NK cells and dendritic cells
  
• Five color-flow cytometry (immunophenotyping of normal and malignant cells; proliferation, activation, apoptosis, necrosis, cytotoxicity; oxidative burst and phagocytosis; intracellular cytokines)
  
• Cytokine secretion assay (detection and enrichment of IFN g secreting cells upon specific or non-specific stimulation)
  
• Detection of CMV specific T cells with tetramers
  
• MTT-Assay (cytostatic drug combination testing)
  
• RT-PCR, Taqman (minimal residual disease monitoring in neuroblastoma)
  
  

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Staff

• Dr. Ruth Esser (NK cells, cell culture, PCR)
  
• Dr. Stephan Klöß (flow cytometry, PCR, cell culture)

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Publications

• Huenecke S, Behl M, Fadler C, Zimmermann SY, Bochennek K, Tramsen L, Esser R, Klarmann D, Kamper M, Sattler A, von Laer D, Klingebiel T, Lehrnbecher T, Koehl U. Age-matched lymphocyte subpopulation reference values in childhood and adolescence: application of exponential regression analysis. Eur J Haematol (2008) Feb 12: Epub ahead of print.
  
• Hollatz G, Grez M, Mastaglio S, Quaritsch R, Huenecke S, Ciceri F, Bonini C, Esser R, Klingebiel T, Kreuter J, Koehl U. T cells for suicide gene therapy: Activation, functionality and clinical relevance. J Immunol Methods (2008);331: 69-81.
  
• Koehl U, Bochennek K, Zimmermann SY, Lehrnbecher T, Sörensen J, Esser R, Andreas C, Kramm C, Grüttner HP, Falkenberg E, Orth A, Bader P, Schwabe D, Klingebiel T. Immune recovery in children undergoing allogeneic stem cell transplantation: absolute CD8+ CD3+ count reconstitution is associated with survival. Bone Marrow Transplant (2007) 39: 269-278.
  
• Ott MG, Schmidt M, Schwarzwaelder K, Stein S, Siler U, Koehl U, Glimm H, Kühlcke K, Schilz A, Kunkel H, Naundorf S, Brinkmann A, Deichmann A, Fischer M, Ball C, Pilz I, Dunbar C, Du Y, Jenkins NA, Copeland NG, Lüthi U, Hassan M, Thrasher AJ, Hoelzer D, von Kalle C, Seger R, Grez M. Correction of X-linked chronic granulomatous disease by gene therapy, augmented by insertional activation of MDS1-EVI1, PRDM16 or SETBP1. Nat Med (2006) 12: 401-409.
  
• Zimmermann SY, Esser R, Rohrbach E, Klingebiel T, Koehl U. A novel four-colour flow cytometric assay to determine natural killer cell or T-cell-mediated cellular cytotoxicity against leukaemic cells in peripheral or bone marrow specimens containing greater than 20% of normal cells. J Immunol Methods (2005) 296: 63-76.
  
• Koehl U, Sörensen J, Esser R, Zimmermann S, Grüttner HP, Tonn T, Seidl C, Seifried E, Klingebiel T, Schwabe D. IL-2 activated NK cell immunotherapy of three children after haploidentical stem cell transplantation. Blood Cells Mol Dis (2004) 33: 261-266.