Identification of a SART-1-derived peptide capable of inducing HLA-A24- restricted and tumor-specific cytotoxic T lymphocytes

Abstract

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-1690-698 peptide (EY-RGFTQDF) 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- 1259+ 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-1690-698 peptide. The SART-1690-698 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-1690-698 peptide was high (> 11200) in both cancer patients and healthy donors. The SART-1690-698 peptide could thus be useful for specific immunotherapy of HLA-A24+ cancer patients.