X-box binding protein 1 (XBP1) (XBP1)

X-box binding protein 1 (XBP1) is a transcription factor that plays a central role in the unfolded protein response (UPR), regulating genes involved in protein folding and quality control (UniProt P17861). The spliced isoform, XBP1s, is an active transcription factor generated by IRE1α-mediated mRNA splicing and is essential for plasma cell differentiation and survival. The specific epitope XBP-1SP367-375 (sequence: YLFPQLISL) is a human leukocyte antigen (HLA)-A2-restricted peptide derived from the C-terminal region of the spliced XBP1 protein (PMID: 21733774). This epitope is highly immunogenic and specifically expressed on the surface of malignant cells in multiple myeloma and certain solid tumors, making it a target for immunotherapy. Therapeutic strategies, such as the multi-peptide vaccine PVX-410, utilize this epitope to induce a cytotoxic T lymphocyte (CTL) response against cancer cells (PMID: 24615718). Targeting this epitope allows for the selective destruction of tumor cells that rely on the XBP1s pathway for survival under endoplasmic reticulum stress. Clinical studies have demonstrated that vaccination with this epitope can expand peptide-specific T cells and show potential clinical activity in patients with smoldering multiple myeloma (NCT01718899).

Other names

XBP-1XBP1sSpliced X-box binding protein 1TREB5Tax-responsive element-binding protein 5XBP1-SP367-375YLFPQLISL

Induction of antigen-specific cytotoxic T lymphocyte (CTL) responses against tumor cells presenting the spliced XBP1 epitope on HLA-A2.