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Identification of potential CTL epitopes of tumor-associated antigen MAGE-1 for five common HLA-A alleles

Identifieur interne : 004932 ( Main/Exploration ); précédent : 004931; suivant : 004933

Identification of potential CTL epitopes of tumor-associated antigen MAGE-1 for five common HLA-A alleles

Auteurs : Esteban Celis [États-Unis] ; John Fikes [États-Unis] ; Peggy Wentworth [États-Unis] ; John Sidney [États-Unis] ; Scott Southwood [États-Unis] ; Ajesh Maewal [États-Unis] ; Marie-France Del Guercio [États-Unis] ; Alessandro Sette [États-Unis] ; Brian Livingston [États-Unis]

Source :

RBID : ISTEX:C37DE553330CB5B6D186684117A95EF2AE1EA05C

English descriptors

Abstract

Abstract: Identification of CTL epitopes for tumor-specific responses is important 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 motifs recognized by the most common HLA-A alleles, and identification of high affinity binding peptides using in vitro quantitative assays. A systematic analysis using the sequence of the product of the tumor-associated MAGE-1 gene has been carried out. All possible peptides of nine 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 quantitative assay. Out of 237 possible peptide/MHC combinations, 47 cases demonstrated good binding affinity (Kd ⩽ 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 for HLA-A3.2,16 for HLA-A11 and five for HLA-A24. Furthermore, eight of these peptides were found to bind well to more than one HLA-A allele. These results have important implications for the development of immunotherapeutic vaccines to treat malignant melanoma.

Url:
DOI: 10.1016/0161-5890(94)90158-9


Affiliations:


Links toward previous steps (curation, corpus...)


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<div type="abstract" xml:lang="en">Abstract: Identification of CTL epitopes for tumor-specific responses is important 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 motifs recognized by the most common HLA-A alleles, and identification of high affinity binding peptides using in vitro quantitative assays. A systematic analysis using the sequence of the product of the tumor-associated MAGE-1 gene has been carried out. All possible peptides of nine 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 quantitative assay. Out of 237 possible peptide/MHC combinations, 47 cases demonstrated good binding affinity (Kd ⩽ 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 for HLA-A3.2,16 for HLA-A11 and five for HLA-A24. Furthermore, eight of these peptides were found to bind well to more than one HLA-A allele. These results have important implications for the development of immunotherapeutic vaccines to treat malignant melanoma.</div>
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