{"created":"2023-03-07T05:14:47.027061+00:00","id":2000861,"links":{},"metadata":{"_buckets":{"deposit":"0a45051c-1e84-4ab9-9a17-47dd8d847eaf"},"_deposit":{"id":"2000861","owners":[1],"pid":{"revision_id":0,"type":"depid","value":"2000861"},"status":"published"},"_oai":{"id":"oai:niigata-u.repo.nii.ac.jp:02000861","sets":["453:455","471:561:562"]},"author_link":[],"item_6_date_granted_51":{"attribute_name":"学位授与年月日","attribute_value_mlt":[{"subitem_dategranted":"2022-03-23"}]},"item_6_degree_grantor_49":{"attribute_name":"学位授与機関","attribute_value_mlt":[{"subitem_degreegrantor":[{"subitem_degreegrantor_language":"ja","subitem_degreegrantor_name":"新潟大学"},{"subitem_degreegrantor_language":"en","subitem_degreegrantor_name":"Niigata University"}],"subitem_degreegrantor_identifier":[{"subitem_degreegrantor_identifier_name":"13101","subitem_degreegrantor_identifier_scheme":"kakenhi"}]}]},"item_6_degree_name_48":{"attribute_name":"学位名","attribute_value_mlt":[{"subitem_degreename":"博士（医学）","subitem_degreename_language":"ja"}]},"item_6_description_4":{"attribute_name":"抄録","attribute_value_mlt":[{"subitem_description":"Background: Synovial sarcoma is a rare malignant soft-tissue tumor that is prevalent in adolescents and young adults, and poor prognosis has been reported in patients with metastatic lesions. Chimeric antigen receptor (CAR) T-cell therapy is an emerging novel therapy for solid tumors; however, its application in synovial sarcoma has not yet been explored. Methods: A novel human epidermal growth factor receptor 2 (HER2)-targeted CAR containing scFv-FRP5, CD8α hinge and transmembrane domains as well as 4-1BB costimulatory and CD3ζ signaling domains was developed. Three synovial sarcoma cell lines that expressed the fusion transcript SS18-SSX1/2/4 were used in the study. Cytokine secretion assay, cytotoxicity assay, and real-time cell analysis experiments were conducted to confirm the function of T cells transduced with the CAR gene. Results: High cell-surface expression of HER2 was observed in all the cell lines. HER2-targeted/4-1BB-costimulated CAR T cells specifically recognized the synovial sarcoma cells, secreted interferon gamma and tumor necrosis factor alpha, and exerted cytotoxic effects in these cells. Conclusion: To the best of our knowledge, this is the first study to indicate that HER2-targeted CAR T cells are directly effective against molecularly defined synovial sarcoma cells. Furthermore, our findings might set the basis for developing improved CAR T cell-based therapies for chemo-refractory or relapsed synovial sarcoma.","subitem_description_language":"en","subitem_description_type":"Abstract"}]},"item_6_description_5":{"attribute_name":"内容記述","attribute_value_mlt":[{"subitem_description":"Translational oncology. 2021, 14(12), 101227.","subitem_description_language":"en","subitem_description_type":"Other"}]},"item_6_description_53":{"attribute_name":"学位記番号","attribute_value_mlt":[{"subitem_description":"新大院博(医)第1075号","subitem_description_language":"ja","subitem_description_type":"Other"}]},"item_6_dissertation_number_52":{"attribute_name":"学位授与番号","attribute_value_mlt":[{"subitem_dissertationnumber":"甲第5005号"}]},"item_6_relation_14":{"attribute_name":"DOI","attribute_value_mlt":[{"subitem_relation_type_id":{"subitem_relation_type_id_text":"https://doi.org/10.1016/j.tranon.2021.101227","subitem_relation_type_select":"DOI"}}]},"item_6_rights_15":{"attribute_name":"権利","attribute_value_mlt":[{"subitem_rights":"© 2021 The Authors. Published by Elsevier Inc.","subitem_rights_language":"en"},{"subitem_rights":"Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International","subitem_rights_language":"en","subitem_rights_resource":"https://creativecommons.org/licenses/by-nc-nd/4.0/"}]},"item_access_right":{"attribute_name":"アクセス権","attribute_value_mlt":[{"subitem_access_right":"open access","subitem_access_right_uri":"http://purl.org/coar/access_right/c_abf2"}]},"item_creator":{"attribute_name":"著者","attribute_type":"creator","attribute_value_mlt":[{"creatorNames":[{"creatorName":"Murayama, Yudai","creatorNameLang":"en"},{"creatorName":"村山, 雄大","creatorNameLang":"ja"}]}]},"item_files":{"attribute_name":"ファイル情報","attribute_type":"file","attribute_value_mlt":[{"accessrole":"open_access","date":[{"dateType":"Available","dateValue":"2023-03-07"}],"displaytype":"detail","filename":"r3nmk1075.pdf","filesize":[{"value":"4.34MB"}],"format":"application/pdf","licensetype":"license_note","mimetype":"application/pdf","url":{"label":"本文","objectType":"fulltext","url":"https://niigata-u.repo.nii.ac.jp/record/2000861/files/r3nmk1075.pdf"},"version_id":"1e7a834c-4f20-4734-9d53-8c076dd06da9"},{"accessrole":"open_access","date":[{"dateType":"Available","dateValue":"2023-03-07"}],"displaytype":"detail","filename":"r3nmk1075_a.pdf","filesize":[{"value":"561KB"}],"format":"application/pdf","licensetype":"license_note","mimetype":"application/pdf","url":{"label":"要旨","objectType":"abstract","url":"https://niigata-u.repo.nii.ac.jp/record/2000861/files/r3nmk1075_a.pdf"},"version_id":"6f77a8d6-7f61-4801-ab9a-eb4981c3a4eb"}]},"item_keyword":{"attribute_name":"キーワード","attribute_value_mlt":[{"subitem_subject":"Synovial sarcoma","subitem_subject_language":"en","subitem_subject_scheme":"Other"},{"subitem_subject":"HER2","subitem_subject_language":"en","subitem_subject_scheme":"Other"},{"subitem_subject":"Chimeric antigen receptor","subitem_subject_language":"en","subitem_subject_scheme":"Other"},{"subitem_subject":"T cell","subitem_subject_language":"en","subitem_subject_scheme":"Other"},{"subitem_subject":"Cancer immunotherapy","subitem_subject_language":"en","subitem_subject_scheme":"Other"}]},"item_language":{"attribute_name":"言語","attribute_value_mlt":[{"subitem_language":"eng"}]},"item_resource_type":{"attribute_name":"資源タイプ","attribute_value_mlt":[{"resourcetype":"doctoral thesis","resourceuri":"http://purl.org/coar/resource_type/c_db06"}]},"item_title":"Effectiveness of 4-1BB-costimulated HER2-targeted chimeric antigen receptor T cell therapy for synovial sarcoma","item_titles":{"attribute_name":"タイトル","attribute_value_mlt":[{"subitem_title":"Effectiveness of 4-1BB-costimulated HER2-targeted chimeric antigen receptor T cell therapy for synovial sarcoma","subitem_title_language":"en"},{"subitem_title":"滑膜肉腫に対するHER2を標的としたCAR-T細胞療法","subitem_title_language":"ja"}]},"item_type_id":"6","owner":"1","path":["455","562"],"pubdate":{"attribute_name":"PubDate","attribute_value":"2023-03-07"},"publish_date":"2023-03-07","publish_status":"0","recid":"2000861","relation_version_is_last":true,"title":["Effectiveness of 4-1BB-costimulated HER2-targeted chimeric antigen receptor T cell therapy for synovial sarcoma"],"weko_creator_id":"1","weko_shared_id":-1},"updated":"2023-03-07T06:31:56.724304+00:00"}