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Tumour Immunology, Cellular & Gene Therapy
The main focus of our work is the analysis of antigen-specific T lymphocyte responses to tumours and the development of immunotherapy approaches for cancer treatment. The transfer of T cell receptor (TCR) genes provides an exciting strategy to equip patient T lymphocytes with well-characterized TCRs, allowing the gene modified T cells to attack tumour cells. We also use the TCR transfer approach to explore whether it can control EBV associated malignancies and CMV spread in immunosuppressed individuals. Our experimental platform involves extensive in vitro analysis of target antigen expression and the definition of effective T cell responses. We use in vivo murine models to test safety and efficacy of new immunotherapy protocols, and are currently translating our research into phase I/II clinical trials with the goal of establishing effective immunity in patients. Currently, the following translational and basic research projects are performed in the Tumour Immunology Research Group: • A clinical phase I/II peptide vaccination trial in leukaemia patients • Construction and validation of retroviral vectors suitable for clinical TCR gene therapy trials in patients with leukaemia and solid tumours • Construction and validation of lentiviral vectors for TCR gene transfer • Analysis of local and systemic T cell responses against tumour-associated antigens in patients with leukaemia and solid tumours • In vivo analysis of TCR gene modified T cells in murine models: mechanisms of CD4 and CD8 T cell interaction, T cell migration, survival and memory development • Production of modified TCRs to prevent pairing with endogenous TCRs • Mapping TCR domains dictating T cell effector function • Assessing the functional activity of TCRs that were affinity matured in vitro by phage display • Analysis of tolerance mechanisms in a TCR transgenic murine model • Use of dendritic cell vaccination strategies in murine models
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