Since the CD28 and 4-1BB domains signal via different pathways, a number of researchers have sought to clarify whether combining the two costimulatory domains in a single CAR might provide synergistic costimulation, resulting in increased expansion and elimination of tumor mass (characteristic of 19-28ζ), and increased durability (characteristic of 19-28ζ) (11). This evidence concerns the gene CD28 and neoplasm.