Lysis of human chondrosarcoma cells by cytolytic T lymphocytes recognizing a MAGE-A3 antigen presented by HLA-A1 molecules.
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.
Bluman
Eric M
EM
Department of Orthopaedic Surgery, Brown University, Providence, Rhode Island, USA.
Coulie
Pierre G
PG
Xiaojuan
Sun
S
Machan
Jason
J
Lin
Chouzao
C
Meitner
Patricia A
PA
Block
Joel A
JA
Terek
Richard M
RM
D017951:Antigen Presentation / Q000276:immunology; D000951:Antigens, Neoplasm / Q000276:immunology*; D001859:Bone Neoplasms / Q000276:immunology* / Q000473:pathology; D045744:Cell Line, Tumor; D002813:Chondrosarcoma / Q000276:immunology* / Q000473:pathology; D000939:Epitopes; D005434:Flow Cytometry; D015788:HLA-A1 Antigen / Q000276:immunology*; D006801:Humans; D007167:Immunotherapy / Q000379:methods*; D007371:Interferon-gamma / Q000494:pharmacology; D009363:Neoplasm Proteins / Q000276:immunology*; D013602:T-Lymphocytes, Cytotoxic / Q000187:drug effects / Q000276:immunology*
D000951:Antigens, Neoplasm; D000939:Epitopes; D015788:HLA-A1 Antigen; C072013:MAGEA3 protein, human; D009363:Neoplasm Proteins; D007371:Interferon-gamma