Lysis of human chondrosarcoma cells by cytolytic T lymphocytes recognizing a MAGE‐A3 antigen presented by HLA‐A1 molecules

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‐γ 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. © 2007 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 25:678–684, 2007