Kurzfassung

The presentation of many tumor- and leukemia-associated antigens at low copy numbers by normal cells and tissues results in the elimination of high-avidity, tumor-reactive T cells from the peripheral T cell repertoire. A promising approach to overcome the limitations imposed by self-tolerance is the adoptive transfer of T cells genetically modified with tumor associated antigen (TAA)-specific TCRs. Tumors have also evolved strategies to evade an effective anti-tumor immune response....
The presentation of many tumor- and leukemia-associated antigens at low copy numbers by normal cells and tissues results in the elimination of high-avidity, tumor-reactive T cells from the peripheral T cell repertoire. A promising approach to overcome the limitations imposed by self-tolerance is the adoptive transfer of T cells genetically modified with tumor associated antigen (TAA)-specific TCRs. Tumors have also evolved strategies to evade an effective anti-tumor immune response. Inhibition of these tumor immune escape mechanisms (e.g. immunosuppressive soluble factors, expansion of regulatory T cells (Treg) as well as myeloid-derived suppressor cells (MDSc)) has the potential to unleash efficient T cell-based anti-tumor cytotoxicity. Our projects focus on the safety (Off- and On-target autoimmunity) and efficacy of p53 TAA-specific TCR-gene therapy in adoptive transfer experiments using humanized mouse models. To address these questions, we implement real-time in vivo bioluminescence and fluorescence to monitor tumor growth and expansion/homing of TCR-transduced effector cells as well as advanced microscopy imaging tool such as 2-photon microscopy to investigate T cell-tumor interaction and the impact of blocking Treg and MDSc suppressive functions on anti-tumor immune response.


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