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Identification of a Gene Coding for a New Squamous Cell Carcinoma Antigen Recognized by the CTL¹

Masanobu Nakao^2,*,§, Shigeki Shichijo^*, Toshihiro Imaizumi^§, Yoshiko Inoue^§, Kazuko Matsunaga^§, Akira Yamada^§, Megumi Kikuchi^§, Naotake Tsuda^§, Keisuke Ohta, Shinzo Takamori, Hideaki Yamana, Hiromasa Fujita and Kyogo Itoh^*,§

Departments of ^* Immunology and Surgery, and Second Department of Anatomy, Kurume University School of Medicine, Fukuoka, Japan; and ^§ Cancer Vaccine Development Division, Kurume University Research Center for Innovative Cancer Therapy, Fukuoka, Japan

Peptide-based specific immunotherapy has resulted in tumor regression in some melanoma patients. However, tumor Ags and peptides for specific immunotherapy, except for treatment of melanomas, have not yet been well identified. In this study, we report a gene encoding a new squamous cell carcinoma (SCC) Ag recognized by cells of the HLA-A24-restricted and tumor-specific CTL line. This gene with 3958-bp length was transcribed from the chromosome 6q22 with six exons, and its mRNA was ubiquitously expressed in both SCCs and normal tissues, and partly expressed in adenocarcinomas. The deduced 958-aa sequence encoded by this gene showed no similarity to any known amino acid sequences. This gene product had a characteristic of an endoplasmic reticulum-resident protein. A 100-kDa protein was detected in the vast majority of SCCs from various tissues, in majority of renal cell carcinomas and brain tumors, and in about one-third of melanomas and adenocarcinomas from various organs other than the breast. In contrast, it was not expressed at all in any of the normal cells or tissues tested, including the testis and fetal liver. Three different peptides at positions 93–101, 161–169, and 899–907 of this Ag were recognized by this CTL line, and all of them induced HLA-A24-restricted and tumor-specific CTLs from PBMCs of SCC patients. Therefore, these peptides may be useful for peptide-based specific immunotherapy of HLA-A24⁺ patients with SCC in various organs, as well as for treatment of other cancer.