Adoptive T cell Therapy Against Solid Tumors: Success Requires Safe TCRs and Countering Immune Evasion

textabstractImmune therapy has proven its feasibility in cancer treatment and in some cases even its preeminence over other treatment modalities such as chemotherapy. Despite promising results observed in clinical trials utilizing or targeting various components of the patient’s own immune system, new challenges emerged as a significant fraction of patients demonstrate inherent or acquired non-responsiveness to therapy or therapy-related toxicity. In this thesis, I provide an overview over pre-clinical approaches we have undertaken in order to optimize T cell receptor (TCR) gene therapy, a treatment that involves genetic introduction of a TCR specific for a selected tumor antigen into patient derived T cells