CD28 and neoplasm: The first CAR would target a tumour-specific antigen and contain the mandatory stimulatory (CD3ζ) and co-stimulatory (e.g. CD28 or CD137) domains, while the second CAR would be specific to an antigen which is typically expressed on normal healthy tissue or bystander cells and linked to inhibitory (iCAR) signalling domains (e.g. PD-1 and CTLA-4).