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

• Subject Area: Clinical Immunology and Allergology ; Hematology, Oncology ; Human Genetics ; Immunology
• Term: from 2015 to 2023
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 256073931

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.

• DFG Programme: Collaborative Research Centres
• Subproject of: SFB 1160: Immune-mediated pathology as a consequence of impaired immune reactions (IMPATH)
• Applicant Institution: Albert-Ludwigs-Universität Freiburg
• Project Heads: Dr. Peter Aichele; Professor Dr. Toni Cathomen; Professor Dr. Stephan Ehl