Peptide-based vaccine therapy, which is designed to elicit T-cell immunity against
tumors, is an attractive approach for the treatment of
cancer patients. To provide a scientific basis for
peptide therapy, an increasing number of CTL-directed
peptides have been identified, and some of them have been tried as
antigen-specific
immunotherapy in the past decade. Only a few studies, however, have been performed on such
peptides restricted with alleles other than
HLA-A2 and -A24. In the present study, we show that immediate early response gene X-1 (IEX-1), a stress-inducible
protein associated with the regulation of cell proliferation and apoptosis, produces antigenic
epitopes recognized by 850B-CTLs, HLA-A33-restricted CTLs newly established from T cells infiltrating into gastric
adenocarcinoma. The IEX-1 gene was highly expressed in most cell lines and tissues from various types of
cancer at both the
mRNA and
protein levels. However, it was not expressed at the
protein level in any normal epithelium or connective tissues tested. Three IEX-1-derived
peptides at positions 47-56, 61-69, and 65-73, which were recognized by the 850B-CTLs, could induce CD8(+)
peptide-specific CTL reaction to
tumor cells from
HLA-A33(+)
gastric cancer patients and other epithelial
cancer patients, but not from healthy donors, in an HLA class I-restricted manner. Because increased expression of IEX-1 is suggested to be involved in the resistance to apoptosis and in the proliferation of
cancer cells, these antigenic
peptides could be potent candidates for
peptide-based specific
immunotherapy against
HLA-A33(+)
gastric cancer and other epithelial
cancers.