Orthotopic T cell receptor replacement by advanced non viral cell engineering (A01)

• Subject Area: Hematology, Oncology ; Immunology ; Rheumatology
• Term: since 2021
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 452881907

Currently used viral-vector-guided recombinant T cell receptor (TCR) expression generates highly variable and therefore unpredictable T cell products in terms of safety and function. In addition, recent data demonstrate that diverse TCR repertoires might be advantageous for long-term therapeutic effects. Advanced genomic engineering tools, like CRISPR Cas9, allow for exact TCR replacement. Such ‘orthotopic TCR replacement’ (OTR) should result in engineered T cells with physiological TCR expression, more predictable functionality and largely reduced potential for toxicity. In this project, OTR T cells will be characterized in vitro and in vivo and developed towards GMP-compliant manufacturing.

• DFG Programme: CRC/Transregios
• Subproject of: TRR 338: LETSIMMUN - Lymphocyte Engineering for Therapeutic Synthetic Immunity
• Applicant Institution: Technische Universität München (TUM)
• Project Head: Professor Dr. Dirk Busch