Identification of a SART-1-derived peptide capable of inducing HLA-A24-restricted and tumor-specific cytotoxic T lymphocytes.
We have described the SART-1 gene-encoding peptides recognized by HLA-A2601-restricted and tumor-specific cytotoxic T lymphocytes (CTLs). We now have investigated whether SART-1 encodes peptides capable of inducing the HLA-A24-restricted CTLs. Among the 18 different peptides with HLA-A24-binding motifs, the SART-1(690-698) peptide (EYRGFTQDF) was most strongly recognized by the HLA-A24-restricted and tumor-specific CTLs established from an esophageal cancer patient. After a third stimulation in vitro, this peptide induced HLA-A24-restricted CTLs recognizing the SART-1(259)+ tumor cells in PBMCs of all HLA-A24 homozygous and the majority of HLA-A24 heterozygous cancer patients and healthy donors tested. A similar activity, induction of CTLs from PBMCs, was observed in the Saccharomyces cerevisiae-derived nonapeptide (EYRGFTPMF) that shares 7 amino acids with the SART-1(690-698) peptide. The SART-1(690-698) peptide-induced CTL activity was significantly higher in PBMCs of HLA-A24 homozygotes than in HLA-A24 heterozygotes. The CTL precursor frequency in PBMCs after a third stimulation in vitro with the SART-1(690-698) peptide was high (>1/200) in both cancer patients and healthy donors. The SART-1(690-698) peptide could thus be useful for specific immunotherapy of HLA-A24+ cancer patients.
Kikuchi
M
M
Cancer Vaccine Development Division of Kurume University Research Center for Innovative Cancer Therapy, Kurume University School of Medicine, Japan.
Nakao
M
M
Inoue
Y
Y
Matsunaga
K
K
Shichijo
S
S
Yamana
H
H
Itoh
K
K
D000951:Antigens, Neoplasm; D002460:Cell Line; D003602:Cytotoxicity, Immunologic; D015234:HLA-A Antigens / Q000276:immunology*; D059871:HLA-A24 Antigen; D006801:Humans; D009363:Neoplasm Proteins / Q000276:immunology*; D009369:Neoplasms / Q000276:immunology* / Q000628:therapy; D010446:Peptide Fragments / Q000276:immunology*; D017411:Ribonucleoproteins, Small Nuclear; D012440:Saccharomyces / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*
D000951:Antigens, Neoplasm; D015234:HLA-A Antigens; D059871:HLA-A24 Antigen; D009363:Neoplasm Proteins; D010446:Peptide Fragments; D017411:Ribonucleoproteins, Small Nuclear; C431323:SART1 protein, human