Paediatric haematology, oncology and haemostaseology -
Dr. phil. nat. Ulrike Köhl

Expertise

Focus of interest is the development and timing of cellular immunotherapies in childhood malignant disease. These include the generation of improved suicide gene transduced T cells for secure donor lymphocyte infusions after allogeneic haematopoetic stem cell transplantation. In a binational phase I trial, the feasibility and safety of high-dose NK cell therapy after mismatched allogeneic stem cell transplantation is investigated. Post transplant, the patients are monitored immunologically and with molecular biologic methods to early recognise graft versus host-disease or relapse.
A second line of interest is concerned with in vitro testing of the interaction of cytotoxic immune cells with new cytostatic drug combinations on leukaemia and embryonal tumour cell lines and with the detection of cytostatic drugs and metabolites in cell preparations and patient samples. A focus is on the cellular and molecular mechanisms of the interaction between allogeneic immune cells and malignant cells.

Resources and Abilities

CliniMACS, AutoMACS, MiniMACS, VarioMACS, SuperMACS (research scale, clinical scale and clinical grade cell selection and depletion from G-CSF stimulated and unstimulated leukaphereses, peripheral blood cell samples, and bone marrow)
Five colour and four colour-flow cytometry (immunophenotyping of normal and malignant cells; proliferation, activation, apoptosis, necrosis, cytotoxicity assays; oxidative burst and phagocytosis; intracellular cytokines)
Cytokine- and phosphoproteine-array
Cytokine secretion assay (detection and enrichment of IFN g secreting cells upon specific or non-specific stimulation)
HPLC (detection and quantitation of cytostatic drugs and metabolites of nucleosid analogues)
MTT-Assay (cytostatic drug combination testing)
RT-PCR, Taqman (minimal residual disease monitoring in neuroblastoma)

Publications

Junker K, Koehl U, Zimmermann S, Stein S, Schwabe D, Klingebiel T, Grez M. Kinetics of cell death in T lymphocytes genetically modified with two novel suicide fusion genes. Gene Ther 2003;10:1189-97
Koehl U, Beck O, Esser R, Seifried E, Klingebiel T, Schwabe D, Seidl C. Quantitative analysis of chimerism after allogeneic stem cell transplantation by PCR amplification of microsatellite markers and capillary electrophoresis with fluorescence detection: The Frankfurt experience. Leukemia 2003;1:232-6
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 in three children after haploidentical stem cell transplantation. Blood Cells, Mol. and Diseases 33: 261-266 (2004)
Zimmermann S, Esser R, Klingebiel T, Koehl U. A novel four-colour-flow cytometric assay to determine NK cell or T cell mediated cellular cytotoxicity against leukemic blasts in peripheral blood or bone marrow specimen containing greater than 20% of normal cells. J Immunol Methods 296: 63-76 (2005)
Passweg JR, Stern M, Koehl U, Uharek L, Tichelli A. Use of natural killer cells in hematopoetic stem cell transplantation. Bone Marrow Transplantation 17: 15-21 (2005).
Bochennek K, Andreas C, Margraf C, Stahlkamp H, Zimmermann S, Esser R, Schwabe D, Klingebiel T, Grüttner HP Koehl U. Hourly monitoring of circulating CD34+ cells to optimize timing of autologous apheresis in pediatric patients. Bone Marrow Transplantation 36, 481-9 (2005).
Koehl U, Esser R, Zimmermann S, Tonn T, Kotchetkov R, Bartling T, Sörensen J, Grüttner HP, Bader P, Seifried E, Martin H, Lang P, Passweg J, Klingebiel T, Schwabe D. Ex vivo expansion of highly purified NK cells for immunotherapy after haploidentical stem cell transplantation in children. Klin Päd 217(6):345-50 (2005).
Beck O, Topp MS, Koehl U, Roilides E, Simitsopoulou M, Hanisch M, Sarfati J, Latge JP, Klingebiel T, Einsele H, Lehrnbecher T. Generation of highly-purified and functionally active human TH1-cells against Aspergillus Fumigatus. Blood (Epub ahead of print)
Beck O, Seidl C, Lehrnbecher T, Kreyenberg H, Schwabe D, Klingebiel T Seifried E, Bader P, Koehl U. Quantification of chimerism within peripheral blood, bone marrow and purified leukocyte subsets: Comparison of singleplex and multiplex PCR amplification of short tandem repeat (STR) loci. Eur J Hematol 76:237-244 (2006)