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Departments of
* Orthopedic Surgery and
Pathology, Sapporo Medical University School of Medicine, and
Department of Clinical Research, Division of Orthopedics, National Sapporo Hospital, Sapporo, Japan;
Department of Orthopedic Surgery, Okayama University Medical School, Okayama, Japan;
¶ Department of Orthopedic Surgery, Chiba Cancer Center Hospital, Chiba, Japan;
|| Department of Orthopedic Surgery, Osaka Medical Center for Cancer and Cardiovascular Diseases, and
# Department of Orthopedics, Osaka University Graduate School of Medicine, Osaka, Japan; and
** Department of Orthopedic Surgery, Cancer Institute Hospital, and
Department of Orthopedic Surgery, National Cancer Center Hospital, Tokyo, Japan
To investigate the immunogenic property of peptides derived from the synovial sarcoma-specific SYT-SSX fusion gene, we synthesized four peptides according to the binding motif for HLA-A24. The peptides, SS391 (PYGYDQIMPK) and SS393 (GYDQIMPKK), were derived from the breakpoint of SYT-SSX, and SS449a (AWTHRLRER) and SS449b (AWTHRLRERK) were from the SSX region. These peptides were tested for their reactivity with CTL precursors (CTLps) in 16 synovial sarcoma patients using HLA-A24/SYT-SSX peptide tetramers and also for induction of specific CTLs from four HLA-A24+ synovial sarcoma patients. Tetramer analysis indicated that the increased CTLp frequency to the SYT-SSX was associated with pulmonary metastasis in synovial sarcoma patients (p < 0.03). CTLs were induced from PBLs of two synovial sarcoma patients using the peptide mixture of SS391 and SS393, which lysed HLA-A24+ synovial sarcoma cells expressing SYT-SSX as well as the peptide-pulsed target cells in an HLA class I-restricted manner. These findings suggest that aberrantly expressed SYT-SSX gene products have primed SYT-SSX-specific CTLps in vivo and increased their frequency in synovial sarcoma patients. The identification of SYT-SSX peptides may offer an opportunity to design peptide-based immunotherapeutic approaches for HLA-A24+ patients with synovial sarcoma.
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