title: Identification of novel helper epitopes of MAGE-A4 tumour antigen: useful tool for the propagation of Th1 cells.
abstract: MAGE-A4 has been considered as an attractive cancer-testis (CT) antigen for tumour immunotherapy. It has been well accepted that T-helper type 1 (Th1) cell-dominant immunity is critical for the successful induction of antitumour immunity in a tumour-bearing host. The adoptive Th1 cell therapy has been shown to be an attractive strategy for inducing tumour eradication in mouse systems. However, Th1-cell therapy using human tumour-specific Th1 cells, which were expanded from peripheral blood mononuclear cells (PBMCs) in a clinically useful protocol, has never been performed. Here, we first identified MAGE-A4-derived promiscuous helper epitope, peptide (MAGE-A4 280-299), bound to both HLA-DPB1(*)0501 and DRB1(*)1403. Using the peptide, we established a suitable protocol for the propagation of MAGE-A4-specific Th1 cells in vitro. Culture of CD4(+) T cells with IFN-gamma-treated PBMC-derived adherent cells in the presence of helper epitope peptide resulted in a great expansion of MAGE-A4-reactive Th cells producing IFN-gamma , but not IL-4. Moreover, it was shown that ligation of MAGE-A4-reactive Th1 cells with the cognate peptide caused the production of IFN-gamma and IL-2. Thus, our identified MAGE-A4 helper epitope peptide will become a good tool for the propagation of tumour-specific Th1 cells applicable to adoptive immunotherapy of human cancer.
authors.affiliation: Division of Immunoregulation, Section of Disease Control, Institute for Genetic Medicine, Hokkaido University, Sapporo, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Ohkuri
authors.forename: D
authors.initials: D
authors.lastname: Wakita
authors.forename: K
authors.initials: K
authors.lastname: Chamoto
authors.forename: Y
authors.initials: Y
authors.lastname: Togashi
authors.forename: H
authors.initials: H
authors.lastname: Kitamura
authors.forename: T
authors.initials: T
authors.lastname: Nishimura
mesh_terms: D000951:Antigens, Neoplasm / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D045744:Cell Line, Tumor; D000939:Epitopes; D006682:HLA-DP Antigens / Q000502:physiology; D059868:HLA-DP beta-Chains; D006801:Humans; D016219:Immunotherapy, Adoptive; D007371:Interferon-gamma / Q000494:pharmacology; D009363:Neoplasm Proteins / Q000276:immunology*; D009369:Neoplasms / Q000628:therapy*; D018417:Th1 Cells / Q000276:immunology*
chemical_list: D000951:Antigens, Neoplasm; D000939:Epitopes; D006682:HLA-DP Antigens; D059868:HLA-DP beta-Chains; C071170:HLA-DPB1 antigen; C095204:MAGEA4 protein, human; D009363:Neoplasm Proteins; D007371:Interferon-gamma