Lysis of human chondrosarcoma cells by cytolytic T lymphocytes recognizing a MAGE-A3 antigen presented by HLA-A1 molecules. |
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Authors: | Eric M Bluman Pierre G Coulie Sun Xiaojuan Jason Machan Chouzao Lin Patricia A Meitner Joel A Block Richard M Terek |
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Affiliation: | Department of Orthopaedic Surgery, Brown University, Providence, Rhode Island, USA. |
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Abstract: | Treatment of chondrosarcomas is limited to resection because these tumors are unresponsive to standard adjuvant treatments, such as chemotherapy and radiation. We have previously shown that high-grade chondrosarcomas express unspecified members of the Melanoma Antigen (MAGE) gene family. We show here that FS human chondrosarcoma (FS) cells express MAGE-A3 gene and HLA-A1 molecules. In vitro assays show that a cytolytic T-lymphocyte clone (CTL) specific for a MAGE-A3 peptide presented by HLA-A1 specifically lysed FS chondrosarcoma cells. Addition of antigenic peptide did not increase the susceptibility of FS cells to CTL mediated lysis, suggesting that HLA-A1 expression by the chondrosarcoma cells limited their susceptibility to lysis by the anti-MAGE-A3 CTL clone. Incubation of FS cells with 50 U/mL interferon-gamma increased surface expression of HLA class-I molecules, increased their susceptibility to lysis, and had no effect on MAGE-A3 gene expression. These results suggest that immunotherapy targeted against chondrosarcoma cells is possible. |
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Keywords: | human chondrosarcoma cells T lymphocytes MAGE‐A3 antigen HLA‐A1 molecules |
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