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Mutated p53 Gene Encodes a Nonmutated Epitope Recognized by HLA-B*4601-restricted and Tumor Cell-reactive CTLs at Tumor Site¹

Departments of Immunology [K. A., S. S., Y. M., T. N., Y. N., K. I.] and Surgery [T. F., K. K.], Kurume University School of Medicine, Kurume 830-0011, Japan

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.

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