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*)

由于移植后大剂量环磷酰胺在预防单倍体移植后GvHD方面受到了极大的关注，新的项目A8将研究类似的、更具体的干预措施来预防GvHD。A8项目将研究宿主反应性t细胞中预防细胞凋亡的重要因素，重点研究Bcl-2家族成员。这些抗凋亡因子将被bh3模拟物、RNAi和CRISPR/Cas9技术靶向。最终目的是开发一种更具体的干预措施来诱导宿主反应性t细胞凋亡。该项目还将在GvL模型中调查此类干预措施的潜在副作用。主要目标是获得最佳的GvHD预防，同时尽量减少白血病复发的风险。

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.