A novel immunogenic CS1-specific peptide inducing antigen-specific cytotoxic T lymphocytes targeting multiple myeloma

Br J Haematol. 2012 Jun;157(6):687-701. doi: 10.1111/j.1365-2141.2012.09111.x. Epub 2012 Apr 26.

Abstract

The CS1 antigen provides a unique target for the development of an immunotherapeutic strategy to treat patients with multiple myeloma (MM). This study aimed to identify HLA-A2(+) immunogenic peptides from the CS1 antigen, which induce peptide-specific cytotoxic T lymphocytes (CTL) against HLA-A2(+) MM cells. We identified a novel immunogenic HLA-A2-specific CS1(239-247) (SLFVLGLFL) peptide, which induced CS1-specific CTL (CS1-CTL) to MM cells. The CS1-CTL showed a distinct phenotype, with an increased percentage of effector memory and activated CTL and a decreased percentage of naïve CTL. CS1(239-247) peptide-specific CD8(+) T cells were detected by DimerX analyses and demonstrated functional activities specific to the peptide. The CTL displayed HLA-A2-restricted and antigen-specific cytotoxicity, proliferation, degranulation and γ-interferon (IFN-γ) production against both primary MM cells and MM cell lines. In addition, the effector memory cells subset (CD45RO(+) CCR7(-) /CD3(+) CD8(+) ) within CS1-CTL showed a higher level of CD107a degranulation and IFN-γ production as compared to effector cells (CD45RO(-) CCR7(-) /CD3(+) CD8(+) ) against HLA-A2(+) primary MM cells or MM cell lines. In conclusion, this study introduced a novel immunogenic HLA-A2-specific CS1(239-247) peptide capable of inducing antigen-specific CTL against MM cells that will provide a framework for its application as a novel MM immunotherapy.

Publication types

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

MeSH terms

  • Antigens, CD / immunology
  • Antigens, Neoplasm / immunology*
  • Antigens, Neoplasm / pharmacology
  • CD8-Positive T-Lymphocytes / immunology*
  • Cancer Vaccines / immunology*
  • Cancer Vaccines / pharmacology
  • Cell Degranulation / drug effects
  • Cell Degranulation / immunology
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • HLA-A2 Antigen / immunology
  • Humans
  • Multiple Myeloma / immunology*
  • Multiple Myeloma / therapy
  • Oligopeptides / immunology*
  • Oligopeptides / pharmacology
  • Receptors, Immunologic / immunology*
  • Signaling Lymphocytic Activation Molecule Family

Substances

  • Antigens, CD
  • Antigens, Neoplasm
  • Cancer Vaccines
  • HLA-A2 Antigen
  • Oligopeptides
  • Receptors, Immunologic
  • SLAMF7 protein, human
  • Signaling Lymphocytic Activation Molecule Family