Prevention of acute Graft-versus-Host disease after allogeneic stem cell transplantation by molecular targeting of anti-apoptotic proteins in activated donor T-cells (A08*)

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As high-dose post-transplantation cyclophosphamide has recently gained an enormous amount of attention for the prevention of GvHD after haploidentical transplantation, the new project A8 will study similar and more specific interventions to prevent GvHD. Project A8 will study the factors important for the prevention of apoptosis in host-reactive T-cells with special emphasis on Bcl-2 family members. These anti-apoptotic factors will then be targeted by BH3-mimetics, RNAi and CRISPR/Cas9 technology. The final aim is to develop a more specific intervention for the induction of apoptosis in host-reactive T-cells. The project will also investigate the potential side effects of such interventions in a GvL model. The main goal is to obtain the best GvHD prevention while minimizing the risk for leukemia relapse.