Mutated p53 gene encodes a nonmutated epitope recognized by HLA-B*4601-restricted and tumor cell-reactive CTLs at tumor site.
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.
Azuma
Koichi
K
Department of Immunology, Kurume University School of Medicine, Kurume 830-0011, Japan.
Shichijo
Shigeki
S
Maeda
Yoshiaki
Y
Nakatsura
Tetsuya
T
Nonaka
Yoichi
Y
Fujii
Teruhiko
T
Koike
Kenta
K
Itoh
Kyogo
K
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*
D018984:Epitopes, T-Lymphocyte; D015235:HLA-B Antigens; C469674:HLA-B*46:01 antigen; D010446:Peptide Fragments; D016159:Tumor Suppressor Protein p53