Detection and induction of CTLs specific for SYT-SSX-derived peptides in HLA-A24(+) patients with synovial sarcoma.
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.
Sato
Yuriko
Y
Department of Orthopedic Surgery, Sapporo Medical University School of Medicine, Japan.
Nabeta
Yuki
Y
Tsukahara
Tomohide
T
Hirohashi
Yoshihiko
Y
Syunsui
Rong
R
Maeda
Akiko
A
Sahara
Hiroeki
H
Ikeda
Hideyuki
H
Torigoe
Toshihiko
T
Ichimiya
Shingo
S
Wada
Takuro
T
Yamashita
Toshihiko
T
Hiraga
Hiroaki
H
Kawai
Akira
A
Ishii
Takeshi
T
Araki
Nobuhito
N
Myoui
Akira
A
Matsumoto
Seiichi
S
Umeda
Tohru
T
Ishii
Seiichi
S
Kawaguchi
Satoshi
S
Sato
Noriyuki
N
D000293:Adolescent; D000328:Adult; D000368:Aged; D000595:Amino Acid Sequence; D019677:Artificial Gene Fusion; D002648:Child; D005260:Female; D015234:HLA-A Antigens / Q000032:analysis* / Q000378:metabolism; D059871:HLA-A24 Antigen; D006412:Hematopoietic Stem Cells / Q000276:immunology; D006801:Humans; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D015514:Oncogene Proteins, Fusion / Q000276:immunology* / Q000378:metabolism; D013584:Sarcoma, Synovial / Q000235:genetics / Q000276:immunology* / Q000628:therapy; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D014178:Translocation, Genetic; D014407:Tumor Cells, Cultured
D015234:HLA-A Antigens; D059871:HLA-A24 Antigen; D015514:Oncogene Proteins, Fusion; C116512:SYT-SSX fusion protein