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...
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| Veröffentlicht in: | The Journal of immunology (1950) 2002-08, Vol.169 (3), p.1611-1618 |
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| creator | Sato, Yuriko Nabeta, Yuki Tsukahara, Tomohide Hirohashi, Yoshihiko Syunsui, Rong Maeda, Akiko Sahara, Hiroeki Ikeda, Hideyuki Torigoe, Toshihiko Ichimiya, Shingo Wada, Takuro Yamashita, Toshihiko Hiraga, Hiroaki Kawai, Akira Ishii, Takeshi Araki, Nobuhito Myoui, Akira Matsumoto, Seiichi Umeda, Tohru Ishii, Seiichi Kawaguchi, Satoshi Sato, Noriyuki |
| description | 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. |
| doi_str_mv | 10.4049/jimmunol.169.3.1611 |
| format | Article |
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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.</description><identifier>ISSN: 0022-1767</identifier><identifier>EISSN: 1550-6606</identifier><identifier>DOI: 10.4049/jimmunol.169.3.1611</identifier><identifier>PMID: 12133991</identifier><language>eng</language><publisher>United States: Am Assoc Immnol</publisher><subject>Adolescent ; Adult ; Aged ; Amino Acid Sequence ; Artificial Gene Fusion ; Child ; Female ; Hematopoietic Stem Cells - immunology ; HLA-A Antigens - analysis ; HLA-A Antigens - metabolism ; HLA-A24 Antigen ; Humans ; Male ; Middle Aged ; Molecular Sequence Data ; Oncogene Proteins, Fusion - immunology ; Oncogene Proteins, Fusion - metabolism ; Sarcoma, Synovial - genetics ; Sarcoma, Synovial - immunology ; Sarcoma, Synovial - therapy ; T-Lymphocytes, Cytotoxic - immunology ; Translocation, Genetic ; Tumor Cells, Cultured</subject><ispartof>The Journal of immunology (1950), 2002-08, Vol.169 (3), p.1611-1618</ispartof><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c378t-8d9f4752a63366cd7f895c1b16232720f3e9c28b4f019744970625d821b071e53</citedby><cites>FETCH-LOGICAL-c378t-8d9f4752a63366cd7f895c1b16232720f3e9c28b4f019744970625d821b071e53</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,777,781,27905,27906</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/12133991$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Sato, Yuriko</creatorcontrib><creatorcontrib>Nabeta, Yuki</creatorcontrib><creatorcontrib>Tsukahara, Tomohide</creatorcontrib><creatorcontrib>Hirohashi, Yoshihiko</creatorcontrib><creatorcontrib>Syunsui, Rong</creatorcontrib><creatorcontrib>Maeda, Akiko</creatorcontrib><creatorcontrib>Sahara, Hiroeki</creatorcontrib><creatorcontrib>Ikeda, Hideyuki</creatorcontrib><creatorcontrib>Torigoe, Toshihiko</creatorcontrib><creatorcontrib>Ichimiya, Shingo</creatorcontrib><creatorcontrib>Wada, Takuro</creatorcontrib><creatorcontrib>Yamashita, Toshihiko</creatorcontrib><creatorcontrib>Hiraga, Hiroaki</creatorcontrib><creatorcontrib>Kawai, Akira</creatorcontrib><creatorcontrib>Ishii, Takeshi</creatorcontrib><creatorcontrib>Araki, Nobuhito</creatorcontrib><creatorcontrib>Myoui, Akira</creatorcontrib><creatorcontrib>Matsumoto, Seiichi</creatorcontrib><creatorcontrib>Umeda, Tohru</creatorcontrib><creatorcontrib>Ishii, Seiichi</creatorcontrib><creatorcontrib>Kawaguchi, Satoshi</creatorcontrib><creatorcontrib>Sato, Noriyuki</creatorcontrib><title>Detection and Induction of CTLs Specific for SYT-SSX-Derived Peptides in HLA-A24+ Patients with Synovial Sarcoma</title><title>The Journal of immunology (1950)</title><addtitle>J Immunol</addtitle><description>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.</description><subject>Adolescent</subject><subject>Adult</subject><subject>Aged</subject><subject>Amino Acid Sequence</subject><subject>Artificial Gene Fusion</subject><subject>Child</subject><subject>Female</subject><subject>Hematopoietic Stem Cells - immunology</subject><subject>HLA-A Antigens - analysis</subject><subject>HLA-A Antigens - metabolism</subject><subject>HLA-A24 Antigen</subject><subject>Humans</subject><subject>Male</subject><subject>Middle Aged</subject><subject>Molecular Sequence Data</subject><subject>Oncogene Proteins, Fusion - immunology</subject><subject>Oncogene Proteins, Fusion - metabolism</subject><subject>Sarcoma, Synovial - genetics</subject><subject>Sarcoma, Synovial - immunology</subject><subject>Sarcoma, Synovial - therapy</subject><subject>T-Lymphocytes, Cytotoxic - immunology</subject><subject>Translocation, Genetic</subject><subject>Tumor Cells, Cultured</subject><issn>0022-1767</issn><issn>1550-6606</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2002</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpNkF2L1DAUhoMo7uzqLxAkV3ohHfPVpLkcZnV3YcCFjqBXIZOeOFnapibtlv33dpkRvTkvB573vXgQekfJWhChPz-Erpv62K6p1Gu-XEpfoBUtS1JISeRLtCKEsYIqqS7QZc4PhBBJmHiNLiijnGtNV2i4hhHcGGKPbd_gu76ZTl_0eLvfZVwP4IIPDvuYcP1zX9T1j-IaUniEBt_DMIYGMg49vt1tig0Tn_C9HQP0Y8ZzGI-4furjY7Atrm1ysbNv0Ctv2wxvz3mFvn_9st_eFrtvN3fbza5wXFVjUTXaC1UyKzmX0jXKV7p09EAl40wx4jlox6qD8IRqJYRWRLKyqRg9EEWh5Ffow2l3SPH3BHk0XcgO2tb2EKdsFNVcCl0tID-BLsWcE3gzpNDZ9GQoMc-izV_RZhFtuHkWvbTen-enQwfNv87Z7AJ8PAHH8Os4hwQmd7ZtF5yaeZ7_m_oDz8CG3A</recordid><startdate>20020801</startdate><enddate>20020801</enddate><creator>Sato, Yuriko</creator><creator>Nabeta, Yuki</creator><creator>Tsukahara, Tomohide</creator><creator>Hirohashi, Yoshihiko</creator><creator>Syunsui, Rong</creator><creator>Maeda, Akiko</creator><creator>Sahara, Hiroeki</creator><creator>Ikeda, Hideyuki</creator><creator>Torigoe, Toshihiko</creator><creator>Ichimiya, Shingo</creator><creator>Wada, Takuro</creator><creator>Yamashita, Toshihiko</creator><creator>Hiraga, Hiroaki</creator><creator>Kawai, Akira</creator><creator>Ishii, Takeshi</creator><creator>Araki, Nobuhito</creator><creator>Myoui, Akira</creator><creator>Matsumoto, Seiichi</creator><creator>Umeda, Tohru</creator><creator>Ishii, Seiichi</creator><creator>Kawaguchi, Satoshi</creator><creator>Sato, Noriyuki</creator><general>Am Assoc Immnol</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope></search><sort><creationdate>20020801</creationdate><title>Detection and Induction of CTLs Specific for SYT-SSX-Derived Peptides in HLA-A24+ Patients with Synovial Sarcoma</title><author>Sato, Yuriko ; Nabeta, Yuki ; Tsukahara, Tomohide ; Hirohashi, Yoshihiko ; Syunsui, Rong ; Maeda, Akiko ; Sahara, Hiroeki ; Ikeda, Hideyuki ; Torigoe, Toshihiko ; Ichimiya, Shingo ; Wada, Takuro ; Yamashita, Toshihiko ; Hiraga, Hiroaki ; Kawai, Akira ; Ishii, Takeshi ; Araki, Nobuhito ; Myoui, Akira ; Matsumoto, Seiichi ; Umeda, Tohru ; Ishii, Seiichi ; Kawaguchi, Satoshi ; Sato, Noriyuki</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c378t-8d9f4752a63366cd7f895c1b16232720f3e9c28b4f019744970625d821b071e53</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2002</creationdate><topic>Adolescent</topic><topic>Adult</topic><topic>Aged</topic><topic>Amino Acid Sequence</topic><topic>Artificial Gene Fusion</topic><topic>Child</topic><topic>Female</topic><topic>Hematopoietic Stem Cells - immunology</topic><topic>HLA-A Antigens - analysis</topic><topic>HLA-A Antigens - metabolism</topic><topic>HLA-A24 Antigen</topic><topic>Humans</topic><topic>Male</topic><topic>Middle Aged</topic><topic>Molecular Sequence Data</topic><topic>Oncogene Proteins, Fusion - immunology</topic><topic>Oncogene Proteins, Fusion - metabolism</topic><topic>Sarcoma, Synovial - genetics</topic><topic>Sarcoma, Synovial - immunology</topic><topic>Sarcoma, Synovial - therapy</topic><topic>T-Lymphocytes, Cytotoxic - immunology</topic><topic>Translocation, Genetic</topic><topic>Tumor Cells, Cultured</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Sato, Yuriko</creatorcontrib><creatorcontrib>Nabeta, Yuki</creatorcontrib><creatorcontrib>Tsukahara, Tomohide</creatorcontrib><creatorcontrib>Hirohashi, Yoshihiko</creatorcontrib><creatorcontrib>Syunsui, Rong</creatorcontrib><creatorcontrib>Maeda, Akiko</creatorcontrib><creatorcontrib>Sahara, Hiroeki</creatorcontrib><creatorcontrib>Ikeda, Hideyuki</creatorcontrib><creatorcontrib>Torigoe, Toshihiko</creatorcontrib><creatorcontrib>Ichimiya, Shingo</creatorcontrib><creatorcontrib>Wada, Takuro</creatorcontrib><creatorcontrib>Yamashita, Toshihiko</creatorcontrib><creatorcontrib>Hiraga, Hiroaki</creatorcontrib><creatorcontrib>Kawai, Akira</creatorcontrib><creatorcontrib>Ishii, Takeshi</creatorcontrib><creatorcontrib>Araki, Nobuhito</creatorcontrib><creatorcontrib>Myoui, Akira</creatorcontrib><creatorcontrib>Matsumoto, Seiichi</creatorcontrib><creatorcontrib>Umeda, Tohru</creatorcontrib><creatorcontrib>Ishii, Seiichi</creatorcontrib><creatorcontrib>Kawaguchi, Satoshi</creatorcontrib><creatorcontrib>Sato, Noriyuki</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>The Journal of immunology (1950)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Sato, Yuriko</au><au>Nabeta, Yuki</au><au>Tsukahara, Tomohide</au><au>Hirohashi, Yoshihiko</au><au>Syunsui, Rong</au><au>Maeda, Akiko</au><au>Sahara, Hiroeki</au><au>Ikeda, Hideyuki</au><au>Torigoe, Toshihiko</au><au>Ichimiya, Shingo</au><au>Wada, Takuro</au><au>Yamashita, Toshihiko</au><au>Hiraga, Hiroaki</au><au>Kawai, Akira</au><au>Ishii, Takeshi</au><au>Araki, Nobuhito</au><au>Myoui, Akira</au><au>Matsumoto, Seiichi</au><au>Umeda, Tohru</au><au>Ishii, Seiichi</au><au>Kawaguchi, Satoshi</au><au>Sato, Noriyuki</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Detection and Induction of CTLs Specific for SYT-SSX-Derived Peptides in HLA-A24+ Patients with Synovial Sarcoma</atitle><jtitle>The Journal of immunology (1950)</jtitle><addtitle>J Immunol</addtitle><date>2002-08-01</date><risdate>2002</risdate><volume>169</volume><issue>3</issue><spage>1611</spage><epage>1618</epage><pages>1611-1618</pages><issn>0022-1767</issn><eissn>1550-6606</eissn><abstract>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.</abstract><cop>United States</cop><pub>Am Assoc Immnol</pub><pmid>12133991</pmid><doi>10.4049/jimmunol.169.3.1611</doi><tpages>8</tpages><oa>free_for_read</oa></addata></record> |
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| source | MEDLINE; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; Alma/SFX Local Collection |
| subjects | Adolescent Adult Aged Amino Acid Sequence Artificial Gene Fusion Child Female Hematopoietic Stem Cells - immunology HLA-A Antigens - analysis HLA-A Antigens - metabolism HLA-A24 Antigen Humans Male Middle Aged Molecular Sequence Data Oncogene Proteins, Fusion - immunology Oncogene Proteins, Fusion - metabolism Sarcoma, Synovial - genetics Sarcoma, Synovial - immunology Sarcoma, Synovial - therapy T-Lymphocytes, Cytotoxic - immunology Translocation, Genetic Tumor Cells, Cultured |
| title | Detection and Induction of CTLs Specific for SYT-SSX-Derived Peptides in HLA-A24+ Patients with Synovial Sarcoma |
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