Engineering of CD3 signaling chains for CAR T cell therapy

T cells expressing Chimeric Antigen Receptors (CARs) are used as cellular therapeutics for cancer patients since several years. Those CAR T cells are able to find and eliminate tumor cells. CARs consist of different building blocks, which are naturally occurring in T cells as part of the T cell receptor complex or in co-stimulatory domains. Additionally, synthetic binding domains are attached that similar to keys- bind to the locks which are expressed on tumor cells. By this means, CAR T cells are able to find and kill tumor cells. Many of the different building blocks of CAR T cells are already well investigated, while others specifically the signaling domains are not well understood. How exactly signaling domains in CAR T cells can bind to signaling proteins, is still under debate. However, those signaling proteins are essential to initiate the signaling cascade within the cells, as soon as CAR T cells bind to the tumor cell. In this project, interactions of signaling proteins with the signaling domains of CARs will be evaluated. This understanding will drive the development of next generation CARs forward.