Identification and characterization of HLA-A24-specific XBP1, CD138 (Syndecan-1) and CS1 (SLAMF7) peptides inducing antigens-specific memory cytotoxic T lymphocytes targeting multiple myeloma

Leukemia. 2018 Mar;32(3):752-764. doi: 10.1038/leu.2017.316. Epub 2017 Nov 1.


X-box binding protein 1 (XBP1), CD138 (Syndecan-1) and CS1 (SLAMF7) are highly expressed antigens in cancers including multiple myeloma (MM). Here, we identify and characterize immunogenic HLA-A24 peptides derived from these antigens for potential vaccination therapy of HLA-A24+ patients with MM. The identified immunogenic HLA-A24-specific XBP1 unspliced (UN)185-193 (I S P W I L A V L), XBP1 spliced (SP)223-231 (V Y P E G P S S L), CD138265-273 (I F A V C L V G F) and CS1240-248 (L F V L G L F L W) peptides induced antigen-specific CTL with anti-MM activity in an HLA-A24 restricted manner. Furthermore, a cocktail containing the four HLA-A24 peptides evoked MM-specific CTL with distinct phenotypic profiles (CD28, CD40L, 41BB, CD38, CD69) and anti-tumor activities, evidenced by perforin upregulation, CD107a degranulation (cytotoxicity) and Th1-type cytokines (IFN-γ/IL-2/TNF-α) production in response to HLA-A24+ MM cells. The multipeptide-specific CTL included antigen-specific memory CD8+ T cells expressing both T-cell activation (CD38, CD69) and immune checkpoints antigens (CTLA, PD-1, LAG-3, TIM-3). These results provide the framework for a multipeptide vaccination therapy to induce tumor-specific CTL in HLA-A24-positive patients with myeloma and other cancers expressing these antigens.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • ADP-ribosyl Cyclase 1 / chemistry
  • ADP-ribosyl Cyclase 1 / immunology*
  • ADP-ribosyl Cyclase 1 / metabolism
  • Amino Acid Sequence
  • Biomarkers
  • Cell Line, Tumor
  • Cytokines / metabolism
  • Cytotoxicity, Immunologic
  • Epitopes, T-Lymphocyte / chemistry
  • Epitopes, T-Lymphocyte / immunology
  • Epitopes, T-Lymphocyte / metabolism
  • HLA-A24 Antigen / genetics
  • HLA-A24 Antigen / immunology*
  • HLA-A24 Antigen / metabolism
  • Humans
  • Immunologic Memory
  • Intercellular Signaling Peptides and Proteins
  • Lymphocyte Activation / immunology
  • Multiple Myeloma / genetics
  • Multiple Myeloma / immunology*
  • Multiple Myeloma / metabolism
  • Peptides / chemistry
  • Peptides / immunology*
  • Peptides / metabolism
  • Phenotype
  • Protein Binding
  • T-Cell Antigen Receptor Specificity / immunology*
  • T-Lymphocytes, Cytotoxic / immunology*
  • T-Lymphocytes, Cytotoxic / metabolism
  • X-Box Binding Protein 1 / chemistry
  • X-Box Binding Protein 1 / immunology*
  • X-Box Binding Protein 1 / metabolism


  • Biomarkers
  • Cytokines
  • Epitopes, T-Lymphocyte
  • HLA-A24 Antigen
  • Intercellular Signaling Peptides and Proteins
  • Peptides
  • X-Box Binding Protein 1
  • XBP1 protein, human
  • CS1 peptide
  • ADP-ribosyl Cyclase 1