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- Title
A Newly Identified MAGE-3-Derived, HLA-A24-Restricted Peptide Is Naturally Processed and Presented as a CTL Epitope on MAGE-3-Expressing Gastrointestinal Cancer Cells.
- Authors
Naoto Miyagawa; Koji Kono; Kousaku Mimura; Hideo Omata; Hidemitsu Sugai; Hideki Fujii
- Abstract
Purpose: In order to broaden the possibility for anti-MAGE-3 immune targeting, it is important to identify HLA-A24-restricted epitopes derived from MAGE-3, since HLA-A24 is one of the most common alleles in Japanese and Asian people. In the present study, we defined a new MAGE-3 derived, HLA-A24-binding peptide presented as a CTL epitope on gastrointestinal cancer cells. Materials and Methods: A panel of MAGE-3-derived peptides (9mer and 10mer) with the HLA-A24-binding motif was selected, and identification of MAGE-3-derived, HLA-A24-restricted CTL epitopes was performed by a reverse immunology approach. To induce MAGE-3-peptide specific CTLs, PBMCs were repeatedly stimulated with monocyte-derived, mature DCs pulsed with the peptides. Subsequent peptide-induced T cells were tested for their specificities by ELISPOT, tetramer and cytotoxic assay. CTL clones were then obtained from the CTL line by limiting dilution. Results: The peptide-inducing CTLs revealed that MAGE-3(113)-peptide was reacted as a CTL epitope in a HLA-A24-restricted fashion, confirmed by ELISPOT and cytotoxic assays. In addition, the MAGE-3(113)-specific CTL clones, confirmed by tetramer assay, showed that the MAGE-3(113) epitope is naturally processed and presented as the CTL epitope on MAGE-3-expressing gastrointestinal cancer cells by evaluating the cold target inhibition assays. Conclusion: The newly identified MAGE-3(113)-peptide epitope is naturally processed and presented as the CTL epitope on MAGE-3-expressing gastrointestinal cancer cells, indicating that anti-MAGE-3 immune targeting with the MAGE-3(113) peptide is a promising approach for treatment. Copyright © 2006 S. Karger AG, Basel
- Subjects
PEPTIDES; EPITOPES; GASTROINTESTINAL diseases; CANCER treatment; CANCER cells
- Publication
Oncology, 2006, Vol 70, Issue 1, p54
- ISSN
0030-2414
- Publication type
Article
- DOI
10.1159/000091185