CD28 and neoplasm: Their extracellular domain is usually an scFv capable of specifically binding antigens overexpressed at the surface of tumor cells, linked to a hinge domain (e.g., CD8, CD28, IgG1, or IgG4) and a transmembrane domain (e.g., CD28, 4-1BB or CD8), fused to one or more variable intracellular costimulatory domains (e.g., CD28, 4-1BB, or OX40 – not present in first generation CARs) and a CD3ζ activation domain, leading to full T cell activation after contact with the target antigen [27].