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

点击翻译按钮获取中文摘要

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.