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*)

通过分子靶向活化供体 T 细胞中的抗凋亡蛋白来预防同种异体干细胞移植后的急性移植物抗宿主病 (A08*)

• 批准号: 278130007
• 金额: --
• 依托单位: Klinik für Hämatologie, Hämostaseologie, Onkologie und Stammzelltransplantation
• 依托单位国家: 德国
• 项目类别: Collaborative Research Centres
• 财政年份: 2015
• 资助国家: 德国
• 起止时间: 2014-12-31 至 2018-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/278130007?language=en
• 关键词: Prevention; acute; Graft; versus; Host

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.

由于移植后高剂量环磷酰胺最近在预防单倍体相合移植后GvHD方面受到了极大的关注，新项目A8将研究类似且更具体的干预措施来预防GvHD。项目A8将研究预防宿主反应性T细胞凋亡的重要因素，特别强调Bcl-2家族成员。然后，这些抗凋亡因子将通过BH 3模拟物、RNAi和CRISPR/Cas9技术靶向。最终目的是开发一种更特异性的干预方法，用于诱导宿主反应性T细胞的凋亡。该项目还将研究GvL模型中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，同时最大限度地降低白血病复发的风险。