A preclinical therapeutic gene editing protocol to restore cytotoxic T cell function in acute haemophagocytic lymphohistiocytosis (A07 (P17))

为了使基因治疗家族性噬血细胞性淋巴组织细胞增生症3型（FHL 3）进入临床应用，建立了两种实验模型：基于患者来源的CD 8 T细胞的体外模型和Jinx小鼠体内疾病模型。该项目旨在通过将缓解诱导免疫化疗与T细胞和基于HSC的基因编辑相结合，建立一种治疗急性HLH过度炎症期间Jinx小鼠的临床相关方案。此外，将建立基于CRISPR-Cpf 1的GMP合规方案，用于在FHL 3患者来源的T细胞中进行离体基因编辑。我们的目标是成功地完成与保罗-埃利希研究所的科学建议会议，以建立一个临床试验。

With the goal to bring gene therapy familial haemophagocytic lymphohistiocytosis type 3 (FHL3) into clinical application, two experimental models have been established: an in vitro model based on patient-derived CD8 T cells and an in vivo disease model in Jinx mice. The project aims at establishing a clinically relevant protocol for treating Jinx mice during acute HLH hyperinflammation by combining remission-inducing immunochemotherapy with T cell and HSC-based gene editing. Furthermore, a CRISPR-Cpf1 based GMP-compliant protocol for ex vivo gene editing in FHL3 patient-derived T cells will be established. The goal is to successfully complete a Scientific Advice Meeting with the Paul-Ehrlich-Institute to set up a clinical trial.