IDENTIFICATION OF POTENTIAL CTL EPITOPES OF TUMOR-ASSOCIATED ANTIGEN MAGE-1 FOR 5 COMMON HLA-A ALLELES

Identification of CTL epitopes for tumor-specific responses is importa nt for the development of immunotherapies to treat cancer patients. We have developed a strategy to identify potential CTL epitopes based on screening of sequences of target proteins for presence of specific mo tifs recognized by the most common HLA-A alleles, and identification o f high affinity binding peptides using in vitro quantitative assays. A systematic analysis using the sequence of the product of the tumor-as sociated MAGE-1 gene has been carried out. All possible peptides of ni ne and ten residues, containing binding motifs for HLA-A1, -A2.1, A-3. 2, -A11 and -A24 were synthesized and tested for binding using a quant itative assay. Out of 237 possible peptide/MHC combinations, 47 cases demonstrated good binding affinity (K-d less than or equal to 500 nM). Several peptides were identified as good MHC binders for each one of the five HLA-A alleles studied (five for HLA-A1, 11 for HLA-A2.1, 10 f or HLA-A3.2, 16 for HLA-A11 and five for HLA-A24. Furthermore, eight o f these peptides were found to bind well to more than one HLA-A allele . These results have important implications for the development of imm unotherapeutic vaccines to treat malignant melanoma.