E5B9 peptide tag (E5B9)

The E5B9 peptide tag is a 10-amino acid epitope (KPLGMYSSNE) derived from the human nuclear autoantigen La/SS-B, which serves as the central targeting component of the modular UniCAR (Universal Chimeric Antigen Receptor) T-cell platform (Bachmann et al., 2014, PMID: 24610416). In this system, T cells are engineered to express a CAR that does not recognize a tumor antigen directly but instead targets the E5B9 peptide. Because the E5B9 epitope is naturally sequestered within the nucleus of healthy cells, it is effectively invisible to UniCAR-T cells under normal conditions, minimizing off-target toxicity (Cartellieri et al., 2016, PMID: 27110505). Therapeutic activity is initiated by the administration of a bispecific Targeting Module (TM), which consists of the E5B9 tag fused to a binding moiety specific for a tumor-associated antigen like CD123 or PSMA. This modular approach allows for the precise control of CAR-T cell activity, as the T cells can be switched off by stopping the infusion of the short-lived TM, thereby providing a significant safety advantage over conventional CAR-T therapies (Arndt et al., 2014, PMID: 25313541). Clinical trials are currently evaluating E5B9-based systems for the treatment of hematologic malignancies and solid tumors, focusing on their ability to manage cytokine release syndrome and improve therapeutic flexibility.

Other names

E5B9 epitopeLa-derived peptide tagLa-epitopeKPLGMYSSNE peptide

The E5B9 peptide tag functions as a universal docking site for modular CAR-T cells. The UniCAR-T cell is engineered with a chimeric antigen receptor specific for the E5B9 epitope. Activation occurs only when a bispecific targeting module (TM) bridges the UniCAR-T cell to a tumor cell by binding the tumor antigen and presenting the E5B9 tag (Bachmann et al., 2014).