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

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.

• Authors: Yasuto Akiyama, Kouji Maruyama, Sachiko Tai, Masaru Komiyama, Akira Iizuka, Masako Takikawa, Chie Ohshita, Akifumi Yamamoto, Naoya Yamazaki, Yoshio Kiyohara, Ken Yamaguchi
• Journal: Anticancer research (Anticancer Res) Vol. 29 Issue 2 Pg. 647-55 (Feb 2009) ISSN: 0250-7005 [Print] Greece
• PMID: 19331215 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• 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

Topics

• 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, immunology)
• T-Lymphocytes, Cytotoxic (immunology)
• Transduction, Genetic