Peptide epitope E5B9 (E5B9)

Peptide epitope E5B9 is a 10-amino acid sequence (KPLPEVTDEY) derived from the human nuclear autoantigen La/SS-B, specifically spanning residues 95-104 [1, 4]. It serves as the central targeting component of the Universal Chimeric Antigen Receptor (UniCAR) platform, a modular and switchable CAR-T cell technology designed to improve the safety and controllability of immunotherapy [3, 9]. In this system, UniCAR T-cells are engineered to express a receptor that specifically recognizes the E5B9 epitope rather than a tumor-associated antigen directly [1, 11]. Therapeutic activity is mediated by 'Target Modules' (TMs), which are bifunctional molecules consisting of the E5B9 epitope fused to a tumor-specific binding moiety, such as a single-chain variable fragment (scFv) or a small molecule [2, 12]. When administered, the TM acts as a bridge, cross-linking the UniCAR T-cells to the tumor cells and triggering T-cell activation and subsequent tumor lysis [4, 5]. This modular approach allows for the precise regulation of T-cell activity by adjusting the dosage or stopping the infusion of the TM, thereby addressing common CAR-T safety concerns like cytokine release syndrome and off-tumor toxicity [11, 12].

Other names

E5B9 epitopeUniCAR epitopeLa/SS-B (95-104) peptideKPLPEVTDEY peptideE5B9 tag

The E5B9 peptide serves as a molecular bridge in the UniCAR system; it is fused to a tumor-targeting moiety to form a Target Module (TM). UniCAR T-cells, which express a chimeric antigen receptor specific for the E5B9 epitope, recognize and bind to the TM, which simultaneously binds to a tumor-associated antigen (TAA) on the cancer cell surface. This interaction forms an immunological synapse, leading to T-cell activation, cytokine release, and targeted tumor cell lysis [3, 4, 12].