Indeed, we detected apparent differences in antigen-induced cytokine release between the novel CAR-T cells targeting HER2, mesothelin and CD19, suggesting that the affinity or additional interaction properties between scFv and the tumor antigen collaborate with other moieties of the CAR to determine the threshold of intracellular signaling that induces CAR-T cell activation.49 This evidence concerns the gene ERBB2 and neoplasm.