Expression of a newly defined tumor-rejection antigen SART3 in musculoskeletal tumors and induction of HLA class I-restricted cytotoxic T lymphocytesby SART3-derived peptides

We recently reported that a SART3 tumor-rejection antigen possessing tumor epitopes is capable of inducing HLA class I-restricted and tumor-specific c ytotoxic T lymphocytes in cancer patients. We studied the expression of the SART3 protein in musculoskeletal tumors to find a molecule For potential u se in tumor-specific immunotherapy. The SART3 was detected at protein level s in 100%, of the osteosarcoma cell lines (n = 20). in 50% of the musculosk eletal tumor. tissue specimens (n = 32). and at notable levels in 67% of os teosarcoma 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 periph eral blood mononuclear cells of patients with osteosarcoma or malignant fib rous histiocytosis. These peptide-induced cytotoxic T lymphocytes recognize d HLA-A24(+) SART3(+) osteosarcoma cells but not HLA-A24(-) or SART3(-) cel ls. These results suggest that the SART3 protein and its derived peptides c ould be molecules appropriate for use in specific immunotherapies for appro ximately 60% of HLA-A24(+) patients with osteosarcoma or malignant fibrous histiocytosis. (C) 2001 Orthopaedic Research Society. Published by Elsevier Science Ltd. All rights reserved.