This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Sasada, T. Articles by Itoh, K. Search for Related Content PubMed PubMed Citation Articles by Sasada, T. Articles by Itoh, K.

Immediate Early Response Gene X-1, a Stress-Inducible Antiapoptotic Gene, Encodes Cytotoxic T-Lymphocyte (CTL) Epitopes Capable of Inducing Human Leukocyte Antigen-A33-Restricted and Tumor-Reactive CTLs in Gastric Cancer Patients

Departments of ¹ Surgery and ² Pathology, Tazuke-Kofukai Kitano Hospital, Osaka; ³ Department of Immunology, Kurume University School of Medicine, Kurume; and ⁴ Department of General Surgery, Hokkaido University Graduate School of Medicine, Sapporo, Japan

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.

This article has been cited by other articles:

				S. L. Sommer, T. J. Berndt, E. Frank, J. B. Patel, M. M. Redfield, X. Dong, M. D. Griffin, J. P. Grande, J. M. A. van Deursen, G. C. Sieck, et al. Elevated blood pressure and cardiac hypertrophy after ablation of the gly96/IEX-1 gene J Appl Physiol, February 1, 2006; 100(2): 707 - 716. [Abstract] [Full Text] [PDF]

				K. Azuma, T. Sasada, H. Takedatsu, H. Shomura, M. Koga, Y. Maeda, A. Yao, T. Hirai, A. Takabayashi, S. Shichijo, et al. Ran, a Small GTPase Gene, Encodes Cytotoxic T Lymphocyte (CTL) Epitopes Capable of Inducing HLA-A33-restricted and Tumor-Reactive CTLs in Cancer Patients Clin. Cancer Res., October 1, 2004; 10(19): 6695 - 6702. [Abstract] [Full Text] [PDF]