Establishment of tumor specific killer T-cells and the cloning of the tumor rejection antigen gene

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We in vestigated the presence of HLA-class I-restricted and tumor-specific CTL in tumor sites of esophageal can cers. HLA-class I-restricted and tumor-specific CTL lines were established from metastatic sites in 5 of 15 patients (Toh et. al., Cell. Immunol. 177 : 137-143,1997). In contrast to these five cases, there was no TIL proliferation in any of four cases of metastatic LN that had undergone prepperative chemotherapy and/or radiation or in six cases of original esophageal tumors. CTL were not generated from lymphocytes of non-metastatic region al LN in any of five patients. These results suggest the existence of HLA-class I-restricted and tumor-specific CTL in tumor sites of esophageal SCC patients who had no preoperative chemotherapy and/or radiation.We have identified a gene encoding tumor antigens from cDNA library of esophageal squamous cell carcinomas (SCCs) recognizes by HLA-A2601-restricted CTLs (Shichijo et al., J.Exp. Med. 187 : 277-288,1998). This gene showed no similarity to known sequences, and encoded two (125 and 43 kD) proteins. The 125 kD protein with leucine-zipper motif was expressed in the nucleus of the majority of proliferating cells tested including normal and malignant cells. The 43 kD protein was expressed in the cytosol of most of SCCs from various organs and half of lung adenocarcinomas, but was not expressed in other cancers nor in a panel of normal tissues. The three nonapeptides in the region shared by the two proteins were recognized by the KE4 CTLs, and one of the peptides induced in vitro from PBMCs the CTLs restricted to the autologous tumor cells. The 43 kD protein and this nonapeptide (KGSGKMKTE) may be useful for specific immunotherapy of HLA-A2601^+ epithelial cancer patients.