E5B9 peptide epitope (E5B9)

The E5B9 peptide epitope is a specific 10-amino acid sequence (KPLPEVTDEY) derived from the human nuclear autoantigen La/SS-B, specifically spanning residues 95 to 104 [2, 8]. It serves as the universal recognition component for the UniCAR (Universal Chimeric Antigen Receptor) platform, a modular approach to CAR T-cell therapy [4, 5]. In this system, T-cells are engineered to express a CAR that targets the E5B9 epitope rather than a tumor-associated antigen directly [4, 7]. Because the E5B9 epitope is cryptic in the native La protein and not naturally exposed on the surface of healthy cells, UniCAR T-cells remain inactive in the absence of an adapter molecule [2, 4]. Therapeutic redirection is achieved using 'Target Modules' (TMs), which are bifunctional proteins consisting of the E5B9 epitope linked to a binding domain specific for a tumor antigen like CD123, PSMA, or FAP [1, 7, 11]. When a TM binds to its tumor target, it presents the E5B9 epitope to the UniCAR T-cells, facilitating an immunological synapse and subsequent tumor cell destruction [5, 6]. This modularity allows for precise control over the intensity and duration of the immune response, as the activity of the UniCAR T-cells can be 'switched off' by discontinuing the administration of the short-lived TMs, thereby improving the safety profile compared to conventional CAR T-cell therapies [2, 8, 11].

Other names

La/SS-B(95-104) epitopeUniCAR epitopeLa epitope E5B9KPLPEVTDEY peptideLupus La protein peptide epitope E5B9

The E5B9 peptide epitope acts as a molecular bridge in the UniCAR system. It is fused to a tumor-specific binding moiety to form a Target Module (TM). UniCAR T-cells, which express a chimeric antigen receptor specific for E5B9, recognize this epitope only when it is presented by the TM on the surface of a tumor cell, triggering T-cell activation and tumor cell lysis.