X-box binding protein 1 (unspliced) (XBP1u)

X-box binding protein 1 (XBP1) is a transcription factor belonging to the basic leucine zipper (bZIP) family and is a critical mediator of the unfolded protein response (UPR) (UniProt P17861). The unspliced form, XBP1u, is typically considered a negative regulator of the spliced, active form (XBP1s), but it also serves as a source of unique antigenic epitopes in certain malignancies (PubMed: 24615718). The specific epitope XBP-1US184-192 is a 9-amino acid peptide (ILLGCLYLA) derived from the unspliced XBP1 protein that is presented by HLA-A*0201 molecules on the surface of cancer cells, particularly in multiple myeloma (PubMed: 22517900). This epitope is utilized as a target in peptide-based cancer vaccines, such as PVX-410, to induce a cytotoxic T-lymphocyte (CTL) response against tumor cells (ClinicalTrials.gov: NCT01718899). By targeting XBP1-derived epitopes, these therapies aim to eliminate plasma cell dyscrasias and other XBP1-overexpressing cancers while leveraging the protein's essential role in plasma cell differentiation and survival (PubMed: 24615718).

Other names

XBP1XBP-1TREB5Tax-responsive element-binding protein 5X-box binding protein 1 unspliced epitope 184-192XBP-1US184-192

Induction of antigen-specific cytotoxic T-lymphocyte (CTL) response against cells presenting the XBP1u epitope on HLA-A2 molecules.