Upon binding of the scFv to CD147 on HCC cells, downstream activation cascades are triggered—mediated by CD28–4-1BB–CD3ζ signaling in T cells and by NKG2D-dependent pathways in NK cells—resulting in cytotoxic degranulation (CD107a expression) and the secretion of proinflammatory cytokines (TNF-α and IFN-γ), which collectively induce apoptosis or lysis of CD147+ HCC cells (145). Here, TNF is linked to hepatocellular carcinoma.