Characterization of a MAGE-1-derived HLA-A24 epitope-specific CTL line from a Japanese metastatic melanoma patient

Anticancer Res. 2009 Feb;29(2):647-55.

Abstract

A MAGE-1 HLA-A24 peptide-specific CTL line was characterized using a novel staining approach in the case of a metastatic melanoma patient who exhibited a remarkable clinical response in HLA-A24 peptide cocktail-pulsed dendritic cell (DCs) vaccine therapy. Briefly, pre- or post-vaccine peripheral blood mononuclear cells (PBMCs) from the vaccinated patient were stimulated several times with MAGE-1 A24 peptide-pulsed DCs and T2-A24 cells in vitro. Expanded MAGE-1 A24-specific CTL line was investigated in terms of immunological functions. The proportion of MAGE-1 A24 tetramer+ CTLs increased from 0.04% to 18.6%, and the absolute numbers of MAGE-1 tetramer+ CTLs increased up to 5,068-fold after stimulations. Expanded CTL line exhibited a strong cytotoxic activity against MAGE-1+ cancer cell line in the restriction of HLA. Finally, successful identification of MAGE-1 A24 peptide-specific T-cell receptor (TCR) cDNA from anti-TCR MoAbsorted CTL was obtained for the first time and the specific cytotoxicity in TCR gene-transduced naive T-cells was confirmed.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Antibodies, Monoclonal / immunology
  • Antigens, Neoplasm / immunology*
  • B-Lymphocytes / immunology
  • Cell Line
  • DNA, Complementary / genetics
  • Dendritic Cells / immunology
  • Epitopes, T-Lymphocyte / immunology*
  • HLA-A Antigens / immunology*
  • HLA-A24 Antigen
  • Humans
  • Interferon-gamma / biosynthesis
  • Melanoma / immunology*
  • Melanoma-Specific Antigens
  • Molecular Sequence Data
  • Neoplasm Proteins / immunology*
  • Peptide Fragments / immunology
  • Receptors, Antigen, T-Cell / genetics
  • Receptors, Antigen, T-Cell / immunology
  • T-Lymphocytes, Cytotoxic / immunology*
  • Transduction, Genetic

Substances

  • Antibodies, Monoclonal
  • Antigens, Neoplasm
  • DNA, Complementary
  • Epitopes, T-Lymphocyte
  • HLA-A Antigens
  • HLA-A24 Antigen
  • MAGEA1 protein, human
  • Melanoma-Specific Antigens
  • Neoplasm Proteins
  • Peptide Fragments
  • Receptors, Antigen, T-Cell
  • Interferon-gamma