Developing polyclonal TCR-T cell therapies using CRISPR base and prime editing (A07*)

• Subject Area: Immunology
• Term: since 2026
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 452881907

Generation of OTR TCR-T cells using advanced genetic engineering with base (BE) and prime editing (PE), enabling the development of multifunctional TCR-T cell therapies that combine the advantages of physiological polyclonal T-cell products with the predictability of engineered monoclonal T cells. To do this, we will optimize the targeted transfer of transgenic TCRs via BE and PE, perform an extensive functional and phenotypical benchmarking of BE/PE-edited versus Cas9-edited OTR-T cells, and establish OTR at the TRBC locus to enable monoallelic integration of transgenic TCRs via pooled delivery of transgenic receptors.

• DFG Programme: CRC/Transregios
• Subproject of: TRR 338: LETSIMMUN - Lymphocyte Engineering for Therapeutic Synthetic Immunity
• Applicant Institution: Technische Universität München (TUM)
• Project Heads: Elvira D' Ippolito, Ph.D.; Dr. Karl Petri