Project Description

The treatment and understanding of cancer is a challenging issue. New approaches like the chimeric antigen receptor (CAR) T-cells showed promising results in fighting cancer by enhancing the killing effects of cytotoxic T-cells. The main benefit of CAR T-cells is their high affinity to tumor antigens, however this raises the issue of possible off-target effects since tumor antigens are not solely expressed on tumor cells but also on healthy tissues (Fesnak et al. 2016; Morgan et al. 2010). In order to avoid off-target effects, we aim to establish CAR T-cell lines which are only activated in the specific tumor microenvironment (Hanahan, Coussens 2012). The T-cells are modified to express CAR controlled by a genetic AND-gate system which needs two inputs from the tumor microenvironment to be activated. This would allow a highly localization restricted binding of cytotoxic T-cells to tumor cells and provide safer cancer cell-based immunotherapy.