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New experimental cancer therapies incorporate the active immunisation with cell-based vaccines, monoclonal antibodies and small molecules which target specific oncogenic mechanisms. Researchers at the CIO Köln Bonn cooperate in this field to better understand the exact workings of these new experimental therapies and to increase the potential for their clinical application.  Ultimately, these activities will lead to tailor-made and patient centred clinical trials.    

The CIO research groups in Köln and Bonn involved in this special area cover a range of cellular and molecular therapies (see illustration). Important themes are the immune activation and immune therapy, therapeutic stem cell modulation, gene therapy approaches using viral vectors and therapies by means of small molecules. 

Immune Activation and Immune Therapy

Associate Professor Michael von Bergwelt-Baildon and Professor Clemens-Martin Wendtner investigate active immune therapeutic  approaches by using CD40 activated and CD40L transduced  B- cells which, with their antigen specific immunological properties especially target CLL cells. Professor Hinrich Abken and Professor Elke Pogge-von Strandmann apply the rational engineering method  to use genetics in active immunotherapies for various malignant entities. Professor Ulrich Herrlinger examines vaccines and gene-therapeutic approaches for malignant glioma in the animal model. Professor Waldemar Kolanus defines new protein functions in T-cell activation and researches the maturing processes of dentritic cells. The projects of Professor Gunther Hartmann and Dr Winfried Barchet utilise the anti-tumour activities of CpG oligodesoxy nucleotides. Dr Marie von Lilienfeld-Toal investigates gamma delta T-cells in multiple myeloma. Professor Percy Knolle researches the mechanisms of immune tolerance origin in CD8 cells and develops molecular techniques which allow the modulation of immune tolerance against metastasising  tumour  cells. Professor Christiane Kuhl develops imaging-based therapeutic approaches. Professor Peter Brossart and Professor Ingo Schmidt-Wolf are specialised in  tumour antigen vaccines as well as dendritic and NKT cells. Professor Joachim Schultze identifies genes in regulatory cells.

Therapeutic Modification of Stem Cells

The research teams of Professor Oliver Brüstle, Dr Viktor Janzen and Professor Dr Björn Scheffler target  the genetic modification of stem cells from different tumours. Professor Harald Neumann carries out  genetic modification of  haematopoietic progenitor cells. The ‘Good Manufacturing Practice’ (GMP) units of Professor Johannes Oldenburg and Professor Birgit Gathof and Associate Professor Christoph Scheid in Köln are of fundamental importance for the clinical development of cell-based experimental therapies for autologous and allogenous stem cell transplantation.

Gene Therapy with Viral Vectors

Improving the understanding of virus mediated gene therapy for cancer and increasing the effectiveness of relevant approaches are the focus of scientific work undertaken in the laboratories of Associate Professor Hildegard Büning, Professor Jürgen Hampl, Professor Christian Drosten, Professor Dr Alexander Pfeifer and Professor Clemens-Martin Wendtner. The research focus of Associate Professor Hildegard Büning lies in the action mechanisms of vectors from the adeno-associated viruses (AAV), which are suitable for a safe transgenic transfer. In this context, this has led to the development of AAV targeting techniques which improve the specificity and effectiveness of AAV-based vectors. Professor  Clemens-Martin Wendtners‘ laboratory utilises the AAV-based vector technology for the development of a clinical gene therapy for chronic lymphocytic leukaemia (CLL). Professor Jürgen Hampl‘s research team analyses strategies for the development of gene therapy in malignant glioma. The group around Professor Alexander Pfeifer is specialised in lentiviral vectors. 

Small Molecule Inhibitors

The groups of Associate Professor Roman Thomas and Dr Günter Krause work in the translational area of improving the understanding of the effectiveness of mechanisms of small molecule inhibitors in oncogenic signal pathways. Professor Thomas, who returned to Köln after his research stay at the Broad Institute of the MIT, Boston, uses genome defined NSCLC cell lines for the response analyses to kinase inhibitors and validation of molecular target structures of these drugs. Dr Günter Krause and Professor Clemens-Martin Wendtner investigate the BCR-triggered signalling and other cellular survival-promoting or pro apoptotic signal pathways in CLL, as well as strategies to therapeutically  influence these signal pathways. The groups of Associate Professor Günter Fingerle-Rowson and Dr Marco Herling work on the identification of new oncogenic signal transduction pathways in CLL and  T-cell lymphomas by validating relevant targets in vitro and in vivo systems (e.g. animal model for CLL), and based on their findings, develop new therapeutic strategies.

Outlook

The strong positioning of the research areas at the CIO Köln Bonn described above, lies in the tight network of different laboratories. Several animal models, through which new therapies can be  tested directly, are established at both locations. Hence, new molecular target regions present a promising starting point for the development of cellular immune therapies and gene therapy –tumour associated anti-genetic structures. In addition, new technologies in gene transfer represent valuable instruments for the development of immunotherapies. Our scientific programs focus on the improvement of the pre-clinical research level to allow the implementation of clinical Phase I studies.    

In this context, the infrastructure of the CIO Köln Bonn with its clinical trials offices and interdisciplinary data management facilities, offers the best conditions  for  the timely translation of pre-clinical research in early clinical studies.

Research Teams for Cellular and Molecular Therapies