A MAGE-1-encoded HLA-A24-binding synthetic peptide induces specific anti-tumor cytotoxic T lymphocytes

Although several MAGE-I peptides have already been identified, the MAGE-I-e ncoded peptide presented by HLA-A24, which is the most common allele in Jap anese population and is also frequently present in Caucasians, might have a wide applicability for immunotherapy using these peptides. To identify thi s potential peptide, we examined the induction of specific cytotoxic T lymp hocytes (CTL) from the peripheral-blood mononuclear cells (PBMC) in HLA-A24 healthy donors by in vitro stimulation with MAGE-I-encoded synthetic pepti des with a binding affinity for HLA-A24, by a simplified method. Of the 5 p eptides tested, the highest HLA binder (NYKHCFPEI) was able to elicit CTL f rom unseparated PBMC by stimulation with freshly isolated, peptide-pulsed P MBC as antigen presenting cells (APC) and by also using interleukin 7 and k eyhole-limpet hemocyanin for a primary culture. The induced CTL could thus lyse HLA-A24 tumor cells expressing MAGE-I, as well as the peptide-pulsed t arget cells, in an HLA-class-I-restricted manner. By using the MAGE-I/HLA-A 24 peptide, NYKHCFPEI, we found it possible to immunize many more patients, especially Japanese patients, by means of such peptide-based immunotherape utic approaches to MAGE-I-positive malignant tumors. (C) 1999 Wiley-Liss, I nc.