CD28 and neoplasm: The latter approach employed engineered CARs composed of an external antigen-binding domain, typically a single-chain variable fragment (scFv) targeting a tumor cell surface antigen, linked to a transmembrane domain and an intracellular-signaling domain, initially limited to the zeta (ζ) chain of the TCR complex [3], and more recently including additional signaling domains such as CD28 and 4-1BB [4, 5].