Expression of a newly defined tumor-rejection antigen SART3 in musculoskeletal tumors and induction of HLA class I-restricted cytotoxic T lymphocytes by SART3-derived peptides.
We recently reported that a SART3 tumor-rejection antigen possessing tumor epitopes is capable of inducing HLA class 1-restricted and tumor-specific cytotoxic T lymphocytes in cancer patients. We studied the expression of the SART3 protein in musculoskeletal tumors to find a molecule for potential use in tumor-specific immunotherapy. The SART3 was detected at protein levels in 100% of the osteosarcoma cell lines (n = 20), in 50% of the musculoskeletal tumor tissue specimens (n = 32), and at notable levels in 67% of osteosarcoma tissues (n = 9) and malignant fibrous histiocytosis tissues (n = 9), respectively. SART3-derived peptides at positions 109-118 and 315-323 induced HLA-A24-restricted tumor-specific cytoxic T lymphocytes from peripheral blood mononuclear cells of patients with osteosarcoma or malignant fibrous histiocytosis. These peptide-induced cytotoxic T lymphocytes recognized HLA-A24+ SART3+ osteosarcoma cells but not HLA-A24 or SART3 cells. These results suggest that the SART3 protein and its derived peptides could be molecules appropriate for use in specific immunotherapies for approximately 60% of HLA-A24+ patients with osteosarcoma or malignant fibrous histiocytosis.
Tsuda
N
N
Department of Immunology, School of Medicine, Kurume University, Japan.
Murayama
K
K
Ishida
H
H
Matsunaga
K
K
Komiya
S
S
Itoh
K
K
Yamada
A
A
D000951:Antigens, Neoplasm / Q000096:biosynthesis*; D001859:Bone Neoplasms / Q000378:metabolism* / Q000473:pathology; D002470:Cell Survival / Q000187:drug effects; D003601:Cytotoxicity Tests, Immunologic; D018219:Histiocytoma, Benign Fibrous / Q000378:metabolism* / Q000473:pathology; D015395:Histocompatibility Antigens Class I / Q000276:immunology; D006801:Humans; D007167:Immunotherapy; D012516:Osteosarcoma / Q000378:metabolism* / Q000473:pathology; D010446:Peptide Fragments / Q000494:pharmacology*; D016601:RNA-Binding Proteins / Q000096:biosynthesis*; D013602:T-Lymphocytes, Cytotoxic / Q000187:drug effects* / Q000276:immunology; D014407:Tumor Cells, Cultured
D000951:Antigens, Neoplasm; D015395:Histocompatibility Antigens Class I; D010446:Peptide Fragments; D016601:RNA-Binding Proteins; C416530:SART3 protein, human