Since most CAR-targeted “tumor associated antigens” are not only expressed by cancer cells but also by healthy cells, combinatorial recognition of two antigens on cancer cells may overcome the risk of severe auto‐immunity. Thus, the identification of molecular mechanisms which result in productive (co‐)synapse formation of two CARs of different specificities and signal complementation of these CARs is necessary. The project builds on our recently developed strategy of combinatorial antigen recognition by two CARs which deliver the primary TCR signal and the CD28 costimulation, respectively.