The present invention relates to a cell which co-expresses a first chimeric antigen receptor (CAR) and second CAR at the cell surface, each CAR comprising: (i) an antigen-binding domain； (ii) a spacer (iii) a trans-membrane domain； and (iv) an endodomain wherein the first CAR is an activating CAR comprising an activating endodomain and the second CAR is an inhibitory CAR comprising a ligation-off inhibitory endodomain； wherein the first CAR binds to a first antigen and the second CAR binds to a second antigen, wherein both the first and second antigens are expressed on the surface of a target cell； wherein the first CAR binds to an epitope on the first antigen which is relatively proximal to the membrane of the target cell, the second CAR binds to an epitope on the second antigen which is relatively distal to the membrane of the target cell, in comparison with the epitope of the first antigen； and wherein the spacer of the first CAR is an equivalent size to the spacer of the second CAR.
