Induction of antitumor cytotoxic T lymphocytes with a MAGE-3-encoded synthetic peptide presented by human leukocytes antigen-A24.
For the development of immunotherapy using MAGE peptides, the identification of additional tumor antigens is required. Because HLA-A24 is the most common allele in Japanese and is also frequently present in Caucasians, MAGE-3-encoded synthetic peptides with binding affinity for HLA-A24 were thus tested for the induction of specific CTLs from the peripheral blood mononuclear cells (PBMCs) of HLA-A24 healthy donors using a simplified method. By using a peptide with a sequence of IMPKAGLLI (amino acid position in MAGE-3 195-203), the CTL responses could thus be induced from unseparated PBMCs by stimulation with freshly isolated, peptide-pulsed PBMCs as antigen-presenting cells (APCs) and by also using interleukin 7 and keyhole limpet hemocyanin for a primary culture. The induced CTLs could lyse HLA-A24 carcinoma cells expressing MAGE-3, as well as the peptide-pulsed target cells, in an HLA class-I restricted manner. The identification of the MAGE-3/HLA-A24 peptide, IMPKAGLLI, may thus potentially offer the opportunities to design peptide-based immunotherapeutic approaches that might prove to be effective in treating patients with MAGE-3-positive malignant tumors.
Tanaka
F
F
Department of Surgery, Medical Institute of Bioregulation, Kyushu University, Beppu, Japan.
Fujie
T
T
Tahara
K
K
Mori
M
M
Takesako
K
K
Sette
A
A
Celis
E
E
Akiyoshi
T
T
D000483:Alleles; D000595:Amino Acid Sequence; D000951:Antigens, Neoplasm / Q000096:biosynthesis / Q000276:immunology*; D001402:B-Lymphocytes; D001665:Binding Sites; D002460:Cell Line; D003110:Colonic Neoplasms; D003602:Cytotoxicity, Immunologic; D004938:Esophageal Neoplasms; D015234:HLA-A Antigens / Q000276:immunology*; D059871:HLA-A24 Antigen; D006801:Humans; D007167:Immunotherapy / Q000379:methods; D007564:Japan; D007938:Leukemia; D009363:Neoplasm Proteins / Q000096:biosynthesis / Q000737:chemistry / Q000276:immunology*; D009842:Oligopeptides / Q000737:chemistry / Q000276:immunology; D016133:Polymerase Chain Reaction; D012016:Reference Values; D013274:Stomach Neoplasms; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D014407:Tumor Cells, Cultured; D044465:White People
D000951:Antigens, Neoplasm; D015234:HLA-A Antigens; D059871:HLA-A24 Antigen; C072013:MAGEA3 protein, human; D009363:Neoplasm Proteins; D009842:Oligopeptides