CD28 and neoplasm: In general, CAR consists of the extracellular single-chain variable fragment (scFv) specific for a cancer marker, and three main domains: an extracellular antigen-binding domain derived from a tumor-specific monoclonal antibody, a transmembrane domain that anchors the CAR to the T cell (derived from CD3, CD4, CD8 or CD28 proteins) and an intracellular T cell activation domain of CD3ζ with one or more costimulatory domains (usually from 4–1BB or CD28) that is required for full T cell activation (32–35).