TNFRSF4 and cancer: The initial attempt at this technology, the first-generation CARs, had a basic structure comprising an extracellular single-stranded variant (scFv) responsible for identifying cancer cells and an intracellular signal transduction domain (CD3 ζ Chain) crucial for cell activation.The intracellular domains of the second and third generation CARs typically include one or two co-stimulatory signaling molecules, such as 4-1BB (CD137), CD28, CD27, OX40 (CD134), inducible T cell co-stimulatory factor (ICOS), or regulatory subunit I anchoring disruptor (RIAD).