There is no one common immunotherapy for the treatment of head and neck cancer (H&N cancer). A streptococcal agent, OK-432, which is classified as a biological response modifier (BRM), is occasionally used by means of local administration for recurrent H&N cancer, and the response rate is approximately 18%. In regard to specific immunotherapy, a murine monoclonal antibody (named mAb 225) against the epidermal growth factor receptor (FGFR) that is frequently overexpressed in H&N cancer has been produced in the U.S.A. Furthermore, to obviate human anti-mouse antibody responses, a chimeric human-to-murine version of mAb 225 (C225) was developed by exchanging the constant regions of mAb 225 to counterparts in human immune globulin. Phase I clinical trials of C225 in the U.S.A. demonstrated that treatment with C225 was well tolerated and that C225 given in combination with cisplatin has biologic activity. On the other hand, many tumor antigens recognized by cytotoxic T lymphocytes (CTL) have been identified from a variety of malignant tumors and some of them, including the MAGE-3 antigen, are frequently expressed in H&N cancer. We identified an MAGE-3-derived epitope recognized by HLA-A24-restricted CTL from peripheral blood mononuclear cells (PBMC). In contrast we failed to generate CTL specific for MAGE-3+/HLA-A24+ tumors from PBMC in any of 5 HLA-A24+ cancer patients whose tumors expressed the MAGE-3 gene. Therefore, we did not apply MAGE-3-derived CTL epitope in clinical uses such as peptide vaccine and peptide pulsed dendritic cell infusion for H&N cancer.