A MAGE-A4 peptide presented by HLA-A2 is recognized by cytolytic T lymphocytes

The MAGE-encoded antigens that are recognized by cytolytic T lymphocytes (C TL) are shared by many tumors and are strictly tumor specific. Clinical tri als involving therapeutic Vaccination of cancer patients with MAGE antigeni c peptides or proteins are in progress. To increase the range of patients e ligible for therapy with peptides, it is important to identify additional M AGE epitopes. We have used a method to identify CTL epitopes, which selects naturally processed peptides. CD8(+) T cells, obtained from individuals wi thout cancer, were stimulated with autologous dendritic cells infected with a recombinant adenovirus containing the MAGE-A4 coding sequence. Responder cell microcultures that specifically lysed autologous EBV-transformed B ce lls infected with vaccinia-MAGE-A4 were cloned using autologous stimulator cells infected with a Yersinia enterocolitica carrying the MAGE-A4 sequence . An anti-MAGE-A4 CTL clone was obtained and the epitope was found to be de capeptide GVYDGREHTV (amino acids 230-239) presented by HLA-A2 molecules. T he CTL clone lysed HLA-A2 tumor cells expressing MAGE-A4. This is the first reported antigenic peptide encoded by MAGE-A4. It may be valuable for canc er immunotherapy because MAGE-A4 is expressed in 51 % of lung carcinomas an d 63 % of esophageal carcinomas, whereas about 50 % of Caucasians and Asian s express HLA-A2.