ERC Starting Grant: EpiTune

Adoptive T cell therapy is a promising approach in various clinical settings, from target-specific immune reconstitution fighting cancer and chronic infections to combating undesired immune reactivity during auto-immunity and after organ transplantation. However, its clinical application is currently hampered by a limited survival and fitness of the T cells after transfer to the patient and the functional plasticity of T cells resulting in possible functional switches (e.g. from immunosuppressive to pro-inflammatory). We showed earlier that epigenetic players such as DNA methylation essentially contribute to T cell differentiation and harbour the unique prospect to imprint a stable developmental and functional state in the genomic structure of a cell. This project aims to utilise the profound impact of epigenetic mechanisms on the senescence process as well as on the functional imprinting of T cells. Using epigenetic manipulations (e.g. CRISPR/ Cas9) during in vitro expansion, we aim to equip the cells with the required properties for their successful and safe therapeutic application.