{"_buckets": {"deposit": "f91c1aa4-6244-499e-a47d-351dd60f6ca1"}, "_deposit": {"id": "2000291", "owners": [1], "pid": {"revision_id": 0, "type": "depid", "value": "2000291"}, "status": "published"}, "_oai": {"id": "oai:niigata-u.repo.nii.ac.jp:02000291", "sets": ["455", "562"]}, "author_link": [], "control_number": "2000291", "item_6_date_granted_51": {"attribute_name": "学位授与年月日", "attribute_value_mlt": [{"subitem_dategranted": "2021-03-23"}]}, "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": "Objectives. One of the reasons as to why chimeric antigen receptors (CAR)-T cell therapy for malignancies other than CD19- or BCMA-positive tumors has yet to produce remarkable progress is the paucity of targetable antigens. NKp44 is only expressed by activated natural killer cells and detects a variety of transformed cells, while it reportedly does not react with normal tissues. The aim of this study is to develop CAR-T cell that can target multiple types of tumor cells. Methods. We created a series of novel CAR constructs in first-generation (1G) and second-generation (2G) CAR format with the extracellular immunoglobulin-like domain of NKp44 (NKp44-CAR). Results. Transduction of the best 1G construct into human primary T cells led to specific cytotoxic effects and cytokine secretion upon encountering multiple types of neoplastic cells including AML, T-ALL and childhood solid tumors. Replacement of the extracellular hinge domain of NKp44 with that of CD8α resulted in diminished CAR function. The 1G NKp44-CAR-T cells exhibited significantly better tumor control in long-term co-culture assays compared with activated NK cells, as well as with NK cells transduced with identical NKp44-CAR. T cells transduced with the best 2G-CAR construct with 4-1BB costimulatory domain proliferated at significantly higher levels upon single antigen exposure and showed significantly better tumor control compared with the 1G-CAR and 2G-CAR with CD28 costimulatory domain. Conclusions. NKp44-based CAR endows T cells with NK cell-like anti-tumor specificity. The CAR gene created in this study will be useful for the development of novel gene-modified T-cell immunotherapy.", "subitem_description_language": "en", "subitem_description_type": "Abstract"}]}, "item_6_description_5": {"attribute_name": "内容記述", "attribute_value_mlt": [{"subitem_description": "Clinical \u0026 Translational Immunology. 2020, 9(7), e1147", "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986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4832号"}]}, "item_6_relation_14": {"attribute_name": "DOI", "attribute_value_mlt": [{"subitem_relation_type_id": {"subitem_relation_type_id_text": "https://doi.org/10.1002/cti2.1147", "subitem_relation_type_select": "DOI"}}]}, "item_6_rights_15": {"attribute_name": "権利", "attribute_value_mlt": [{"subitem_rights": "【○!C】 2020 The Authors.", "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": "Kasahara, Yasushi", "creatorNameLang": "en"}, {"creatorName": "笠原, 靖史", "creatorNameLang": "ja"}]}]}, "item_files": {"attribute_name": "ファイル情報", "attribute_type": "file", "attribute_value_mlt": [{"date": [{"dateType": "Available", "dateValue": "2022-04-04"}], "displaytype": "detail", "download_preview_message": "", "file_order": 0, "filename": "r2nmk986.pdf", "filesize": [{"value": "4.69MB"}], "format": "application/pdf", "future_date_message": "", "is_thumbnail": false, "licensetype": "license_free", "mimetype": "application/pdf", "size": "4.69MB", "url": {"label": "本文", "objectType": "fulltext", "url": "https://niigata-u.repo.nii.ac.jp/record/2000291/files/r2nmk986.pdf"}, "version_id": "96c9961b-62a5-4ca9-ae00-923af3bb627a"}, {"date": [{"dateType": "Available", "dateValue": "2022-04-04"}], "displaytype": "detail", "download_preview_message": "", "file_order": 1, "filename": "r2nmk986_a.pdf", "filesize": [{"value": "546KB"}], "format": "application/pdf", "future_date_message": "", "is_thumbnail": false, "licensetype": "license_free", "mimetype": "application/pdf", "size": "546KB", "url": {"label": "要旨", "objectType": "abstract", "url": "https://niigata-u.repo.nii.ac.jp/record/2000291/files/r2nmk986_a.pdf"}, "version_id": "3a981e16-3529-47b3-9e05-dbc489864ec1"}]}, "item_keyword": {"attribute_name": "キーワード", "attribute_value_mlt": [{"subitem_subject": "acute myeloid leukaemia", "subitem_subject_language": "en", "subitem_subject_scheme": "Other"}, {"subitem_subject": "chimeric antigen receptor", "subitem_subject_language": "en", "subitem_subject_scheme": "Other"}, {"subitem_subject": "natural killer cell", "subitem_subject_language": "en", "subitem_subject_scheme": "Other"}, {"subitem_subject": "NKp44", "subitem_subject_language": "en", "subitem_subject_scheme": "Other"}, {"subitem_subject": "paediatric solid tumors", "subitem_subject_language": "en", "subitem_subject_scheme": "Other"}, {"subitem_subject": "T-cell acute lymphoblastic leukaemia", "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": "Development and characterisation of NKp44-based chimeric antigen receptors that confer T cells with NK cell-like specificity", "item_titles": {"attribute_name": "タイトル", "attribute_value_mlt": [{"subitem_title": "Development and characterisation of NKp44-based chimeric antigen receptors that confer T cells with NK cell-like specificity", "subitem_title_language": "en"}, {"subitem_title": "NK細胞様の特性をT細胞に付与するNKp44を用いたキメラ抗原受容体の開発と評価", "subitem_title_language": "ja"}]}, "item_type_id": "6", "owner": "1", "path": ["455", "562"], "permalink_uri": "http://hdl.handle.net/10191/0002000291", "pubdate": {"attribute_name": "PubDate", "attribute_value": "2022-04-04"}, "publish_date": "2022-04-04", "publish_status": "0", "recid": "2000291", "relation": {}, "relation_version_is_last": true, "title": ["Development and characterisation of NKp44-based chimeric antigen receptors that confer T cells with NK cell-like specificity"], "weko_shared_id": -1}