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Induction of Antitumor Cytotoxic T Lymphocytes with a MAGE-3-encoded Synthetic Peptide Presented by Human Leukocytes Antigen-A24¹

Department of Surgery, Medical Institute of Bioregulation, Kyushu University [F. T., T. F., K. T., M. M., T. A.], Beppu, 874, Japan; Biotechnology Research Laboratories, Takara Shuzo Co., Ltd. [K. T.], Otsu, Shiga 520-21, Japan; and Cytel Corporation, San Diego, California 92121 [A. S., E. S.]

For the development of immunotherapy using MAGE peptides, the identification of additional tumor antigens is required. Because HLA-A24 is the most common allele in Japanese and is also frequently present in Caucasians, MAGE-3-encoded synthetic peptides with binding affinity for HLA-A24 were thus tested for the induction of specific CTLs from the peripheral blood mononuclear cells (PBMCs) of HLA-A24 healthy donors using a simplified method. By using a peptide with a sequence of IMPKAGLLI (amino acid position in MAGE-3 195–203), the CTL responses could thus be induced from unseparated PBMCs by stimulation with freshly isolated, peptide-pulsed PBMCs as antigen-presenting cells (APCs) and by also using interleukin 7 and keyhole limpet hemocyanin for a primary culture. The induced CTLs could lyse HLA-A24 carcinoma cells expressing MAGE-3, as well as the peptide-pulsed target cells, in an HLA class-I restricted manner. The identification of the MAGE-3/HLA-A24 peptide, IMPKAGLLI, may thus potentially offer the opportunities to design peptide-based immunotherapeutic approaches that might prove to be effective in treating patients with MAGE-3-positive malignant tumors.

¹ This work was supported by Grants-in-Aid for Scientific Research (08557074 and 09470253) from the Ministry of Education, Science, Sports and Culture, Japan.

² To whom requests for reprints should be addressed, at Department of Surgery, Medical Institute of Bioregulation, Kyushu University, 4546 Tsurumihara, Beppu 874, Japan. Phone: 81-977-27-1650; Fax: 81-977-27-1607.

Received 8/ 8/97. Accepted 8/29/97.

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