title: Mutated p53 gene encodes a nonmutated epitope recognized by HLA-B*4601-restricted and tumor cell-reactive CTLs at tumor site.
abstract: Mutations of p53 gene occur in approximately 50% of human cancers, and accumulated p53 protein may be an appropriate target molecule to use for cancer immunotherapy. Indeed, mutated or nonmutated p53-derived peptides can induce HLA class I-restricted and tumor cell-reactive CTLs in vitro. However, to our knowledge, evidence that p53-derived peptides are truly recognized by CTLs at tumor sites has not yet been obtained. This study revealed that a mutated p53 gene encoded a nonmutated nonapeptide recognized by a HLA-B46-restricted and tumor cell-reactive CTL line that was established from T cells infiltrating a colon cancer lesion with the p53 mutation. This p53 peptide, at amino acid positions 99-107, had the ability to induce HLA-B46-restricted and peptide-specific CTLs reactive to tumor cells with the p53 mutation from the peripheral blood mononuclear cells of cancer patients, but not from those of healthy donors. These peptide-induced CTLs did not react to either HLA-B46(+) tumor cells without the p53 mutation or to HLA-B46(+) phytohemagglutinin-blastoid cells. These results provide a scientific basis for the development of p53-directed specific immunotherapy for HLA-B46(+) cancer patients.
authors.affiliation: Department of Immunology, Kurume University School of Medicine, Kurume 830-0011, Japan.
authors.forename: Koichi
authors.initials: K
authors.lastname: Azuma
authors.forename: Shigeki
authors.initials: S
authors.lastname: Shichijo
authors.forename: Yoshiaki
authors.initials: Y
authors.lastname: Maeda
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Nakatsura
authors.forename: Yoichi
authors.initials: Y
authors.lastname: Nonaka
authors.forename: Teruhiko
authors.initials: T
authors.lastname: Fujii
authors.forename: Kenta
authors.initials: K
authors.lastname: Koike
authors.forename: Kyogo
authors.initials: K
authors.lastname: Itoh
mesh_terms: D000818:Animals; D019556:COS Cells; D002522:Chlorocebus aethiops; D018984:Epitopes, T-Lymphocyte / Q000235:genetics / Q000276:immunology*; D005260:Female; D016158:Genes, p53 / Q000276:immunology*; D015235:HLA-B Antigens / Q000235:genetics / Q000276:immunology*; D006801:Humans; D008213:Lymphocyte Activation; D008297:Male; D009369:Neoplasms / Q000235:genetics / Q000276:immunology*; D010446:Peptide Fragments / Q000235:genetics / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D014162:Transfection; D014407:Tumor Cells, Cultured; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000276:immunology*
chemical_list: D018984:Epitopes, T-Lymphocyte; D015235:HLA-B Antigens; C469674:HLA-B*46:01 antigen; D010446:Peptide Fragments; D016159:Tumor Suppressor Protein p53