{"created":"2022-04-04T06:58:48.333564+00:00","id":2000291,"links":{},"metadata":{"_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":["453:455","471:561:562"]},"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 & 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","filename":"r2nmk986.pdf","filesize":[{"value":"4.69MB"}],"format":"application/pdf","licensetype":"license_note","mimetype":"application/pdf","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","filename":"r2nmk986_a.pdf","filesize":[{"value":"546KB"}],"format":"application/pdf","licensetype":"license_note","mimetype":"application/pdf","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"],"pubdate":{"attribute_name":"PubDate","attribute_value":"2022-04-04"},"publish_date":"2022-04-04","publish_status":"0","recid":"2000291","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_creator_id":"1","weko_shared_id":-1},"updated":"2022-12-15T04:29:15.915054+00:00"}