A multiepitope of XBP1, CD138 and CS1 peptides induces myeloma-specific cytotoxic T lymphocytes in T cells of smoldering myeloma patients

Leukemia. 2015 Jan;29(1):218-29. doi: 10.1038/leu.2014.159. Epub 2014 May 14.


We evaluated a cocktail of HLA-A2-specific peptides including heteroclitic XBP1 US184-192 (YISPWILAV), heteroclitic XBP1 SP367-375 (YLFPQLISV), native CD138260-268 (GLVGLIFAV) and native CS1239-247 (SLFVLGLFL), for their ability to elicit multipeptide-specific cytotoxic T lymphocytes (MP-CTLs) using T cells from smoldering multiple myeloma (SMM) patients. Our results demonstrate that MP-CTLs generated from SMM patients' T cells show effective anti-MM responses including CD137 (4-1BB) upregulation, CTL proliferation, interferon-γ production and degranulation (CD107a) in an HLA-A2-restricted and peptide-specific manner. Phenotypically, we observed increased total CD3(+)CD8(+) T cells (>80%) and cellular activation (CD69(+)) within the memory SMM MP-CTL (CD45RO(+)/CD3(+)CD8(+)) subset after repeated multipeptide stimulation. Importantly, SMM patients could be categorized into distinct groups by their level of MP-CTL expansion and antitumor activity. In high responders, the effector memory (CCR7(-)CD45RO(+)/CD3(+)CD8(+)) T-cell subset was enriched, whereas the remaining responders' CTL contained a higher frequency of the terminal effector (CCR7(-)CD45RO(-)/CD3(+)CD8(+)) subset. These results suggest that this multipeptide cocktail has the potential to induce effective and durable memory MP-CTL in SMM patients. Therefore, our findings provide the rationale for clinical evaluation of a therapeutic vaccine to prevent or delay progression of SMM to active disease.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Cell Proliferation
  • DNA-Binding Proteins / immunology*
  • Disease Progression
  • Epitopes / immunology*
  • Female
  • Humans
  • Immunologic Memory
  • Intercellular Signaling Peptides and Proteins
  • Male
  • Middle Aged
  • Multiple Myeloma / immunology*
  • Multiple Myeloma / metabolism
  • Multiple Myeloma / pathology
  • Peptides / immunology*
  • Regulatory Factor X Transcription Factors
  • Syndecan-1 / immunology*
  • T-Lymphocytes, Cytotoxic / cytology
  • T-Lymphocytes, Cytotoxic / immunology*
  • Transcription Factors / immunology*
  • X-Box Binding Protein 1


  • DNA-Binding Proteins
  • Epitopes
  • Intercellular Signaling Peptides and Proteins
  • Peptides
  • Regulatory Factor X Transcription Factors
  • SDC1 protein, human
  • Syndecan-1
  • Transcription Factors
  • X-Box Binding Protein 1
  • XBP1 protein, human
  • CS1 peptide