HLA-A*02:01-presented Syndecan-1 (260-268) epitope (HLA-A2/CD138(260-268))

The HLA-A2–presented CD138(260-268) epitope is a peptide-major histocompatibility complex (pMHC) target consisting of a 9-amino acid fragment (GLVGLIFAV) derived from the Syndecan-1 protein, presented by the HLA-A*02:01 molecule. Syndecan-1, or CD138, is a transmembrane proteoglycan that is characteristically overexpressed on the surface of malignant plasma cells, serving as a diagnostic marker and therapeutic target in multiple myeloma (Bae et al., 2011, Leukemia). This specific epitope is processed intracellularly and presented on the cell surface, where it can be recognized by the T-cell receptors (TCRs) of CD8+ cytotoxic T lymphocytes (CTLs). Targeting this pMHC complex allows for the development of highly specific immunotherapies, such as TCR-engineered T cells (TCR-T) and peptide vaccines like PVX-410, which aim to induce a robust anti-tumor immune response while sparing non-expressing tissues (NCT01718899). Clinical interest in this target stems from its potential to overcome the limitations of traditional monoclonal antibodies by engaging the cellular arm of the immune system. However, therapeutic development must account for the expression of CD138 on some normal epithelial tissues to avoid on-target, off-tumor toxicity. As a tumor-associated antigen (TAA), the HLA-A2/CD138(260-268) complex remains a significant focus for precision medicine in hematologic malignancies.

Other names

HLA-A*02:01/CD138(260-268)Syndecan-1 (260-268) peptideGLVGLIFAV peptideCD138-260 epitopeHLA-A2-restricted CD138 epitope

The target is recognized by specific T-cell receptors (TCRs) on CD8+ T cells, which triggers the formation of an immunological synapse and the subsequent release of cytotoxic granules (perforin and granzymes) to induce apoptosis in the target cell.