Lay summary
Cancer treatment has been revolutionised by the engineering of patient T cells ex vivo with artificial T cell receptors (CAR) that hardwire T cells to attack cancer cells. CAR T cells target proteins expressed on the surface of tumour cells, leading to destruction of the cancer. However, up to 25% of lymphoma / leukaemia patients may develop resistance to CAR T cell therapy. This happens when tumours lose expression of the tumour antigen. Our proposal will circumvent this by allowing CART cells to target a second tumour antigen. The novel genetic mechanism of targeting the second tumour antigen has been designed for optimal production and activity of the CAR T cells.