HLA-A*02:01-presented X-box binding protein 1 unspliced (184-192) epitope (HLA-A2/XBP-1US184-192)

The HLA-A2–presented XBP-1US184-192 epitope is a peptide-major histocompatibility complex (pMHC) target consisting of a 9-amino acid sequence (YISPWILAV) derived from the unspliced form of X-box binding protein 1 (XBP-1) presented by the HLA-A*02:01 allele (Bae et al., 2011). XBP-1 is a transcription factor that plays a pivotal role in the unfolded protein response (UPR) and is essential for the differentiation and survival of plasma cells (Bae et al., 2015). In multiple myeloma and other plasma cell dyscrasias, XBP-1 is frequently overexpressed, leading to the presentation of this specific epitope on the surface of malignant cells. This makes the epitope a viable target for T-cell-based immunotherapies, including therapeutic vaccines and T-cell receptor (TCR) engineered T-cells. For instance, the multi-peptide vaccine PVX-410 includes this epitope to induce a robust cytotoxic T-lymphocyte (CTL) response against myeloma cells (ClinicalTrials.gov NCT01718899). Targeting this pMHC complex allows for high specificity, as it leverages the intracellular proteome of the cancer cell, which is otherwise inaccessible to traditional antibody-based therapies.

Other names

XBP-1US184-192 peptideXBP1 unspliced 184-192 epitopeYISPWILAV peptideHLA-A*02:01/XBP1-US(184-192)XBP1-US184 epitope

Induction of peptide-specific cytotoxic T-lymphocyte (CTL) response and direct lysis of epitope-presenting cells.