{"created":"2023-07-27T07:01:15.755868+00:00","id":61487,"links":{},"metadata":{"_buckets":{"deposit":"c23c9eda-8b95-4f25-8b5f-50e23654656b"},"_deposit":{"created_by":18,"id":"61487","owners":[18],"pid":{"revision_id":0,"type":"depid","value":"61487"},"status":"published"},"_oai":{"id":"oai:kanazawa-u.repo.nii.ac.jp:00061487","sets":["2812:2813:2845"]},"author_link":["21834","92452"],"item_9_biblio_info_8":{"attribute_name":"書誌情報","attribute_value_mlt":[{"bibliographicIssueDates":{"bibliographicIssueDate":"1993-03-25","bibliographicIssueDateType":"Issued"},"bibliographicPageStart":"3p.","bibliographicVolumeNumber":"1987 – 1988","bibliographic_titles":[{"bibliographic_title":"昭和63(1988)年度 科学研究費補助金 一般研究(B) 研究成果報告書概要"},{"bibliographic_title":"1988 Fiscal Year Final Research Report Summary","bibliographic_titleLang":"en"}]}]},"item_9_creator_33":{"attribute_name":"著者別表示","attribute_type":"creator","attribute_value_mlt":[{"creatorNames":[{}],"nameIdentifiers":[{},{},{}]}]},"item_9_description_21":{"attribute_name":"抄録","attribute_value_mlt":[{"subitem_description":"1)マウス神経芽細胞腫C1300にレトロウイルスベクタ-PSVX(MuγΔA)を用いてIFN-γ遺伝子を導入した腫瘍細胞の、MHCをはじめとする表面抗原の発現ならびに腫瘍細胞を皮下に接種した場合の宿主の反応を検討した。IFN-γ遺伝子が入った細胞を皮下接種すると、親株に比べ腫瘍の増大が極端に低下し、2.4x10個の細胞の接種でも生着龍は7%程度であった。腫瘍の直径で皮下腫瘍の成長をみると、親株がほぼ直線的に増大するに対してIFN-γ遺伝子をいれた腫瘍株は14-20日目に一時腫瘍増大が停止し、その時期に拒絶されるものも現れ宿主の免疫反応の活性化が示唆された。生存曲線でみてもIFN-γ遺伝子導入腫瘍担体マウスは生存日数の延長がみられた。\n2)次いで、マウス203gliomaに対するCTLクロ-ン、E-4、を作成し、そのCTLにretrovirus vectorを用いて、同様の方法によたマウスIFN-γcDNAを導入し、その抗腫瘍活性を増強させることを試みた。G412にて選択されたsubclone,E-γ-4,E-γ-5,E-γ-6,E-γ-7,E-γ-9を樹立した。Southerm blot法でこれらsubcloneにIFN-γ遺伝子が組み込まれていることが確認された。Cr(51) release assayでin vitroでの抗腫瘍活性を検討すると、CTL親株であるE-4に比較して、IFN-γ遺伝子を組み込んだsubline,特にE-γ-9では、killing activityは約3倍上昇していた。in vivoのWinn assayにおいても、親株であるE-4に比較して、生着率の抑制に有意の効果が認められた。\n3)以上の所見より、マウス神経計腫瘍のシステムにおいて、腫瘍細胞および腫瘍特異的キラ-T細胞にIFN-γ遺伝子を組み込むことが可能であり、そのことによって、抗腫瘍免疫反応をmodifyすることが可能であることが明らかとなった。このような手法が、将来的には、ヒト悪性脳腫瘍の治療にも応用できる可能性が示唆された。","subitem_description_type":"Abstract"},{"subitem_description":"A mouse ihterfebon (IFN) gamma CDNA was transferred to mouse neuroblastoma cell line, C1300 of A/Jax origin, with a chimeric retrovirus containing the IFN gamma gene. Two infected subclones C-gamma-3 and C-gamma-22 were obtained as a low and a high producers, respectively. These subclones were similar to the original clone in respects of in vitro growth pattern, morphology, and antigen expression of neurofilaments, except the expression of major hisiocompatibility complex (MHC) class I antigens, which were extremely augmented at the surface expression level as well as at the transcription level, regardless the difference in amount of their IFN-gamma production. The in vivo tumorigenicity was reduced in the high producer, C-gamma-22, but not in the low producer, C-gamma-3. The in vivo tumor growth rate was suppressed in both subclones, as compared to the parental line. It was therefore suggested that the suppression of tumor formation is more closely associated with constitutive IFN-gamma production rather than the MHC antigen expression, and that the tumor growth rate is affected by the high expression of the surface antigens.\nAs a next step, the cDNA encoding mouse IFN-gamma was transferred into a specific cytotoxic T lymphocyte (CTL) clone, designated E-4, against 203-glioma (a 20- methylcholanthrene-induced glioma line of C57/BL mouse origin). The efficacy of IFN-gamma production from the exogenous gene on augumeniation of tumor targeting was confirmed. Out of five, two gene-transferred subclones constitutively produced 8 to 10 times higher amount of IFN-gamma as compared with the parental E-4. Correspondingly, these two subclones exhibited 2 to 3 times higher killing activity against 203-glioma as compared with the parental line. It was thought that tumor cells, in the vicinity of the constitutively IFN-gamma-producing CTLs, may be stimulated to induce or enhance the expression of surface antigens, including the MHC antigens as well as the tumor associated antigens relevant to immune recognition.\nIn summary, it was hopefully suggested that retrovirus-mediated transfer of cytokine genes would be useful for a modified immunotherapy of cancer.","subitem_description_type":"Abstract"}]},"item_9_description_22":{"attribute_name":"内容記述","attribute_value_mlt":[{"subitem_description":"研究課題/領域番号:62480307, 研究期間(年度):1987 – 1988","subitem_description_type":"Other"},{"subitem_description":"出典：研究課題「遺伝子操作により効果を増強したキラ-T細胞による脳腫瘍に対する養子免疫療法の開発」課題番号62480307\n（KAKEN：科学研究費助成事業データベース（国立情報学研究所）） \n（https://kaken.nii.ac.jp/ja/report/KAKENHI-PROJECT-62480307/624803071989kenkyu_seika_hokoku_gaiyo/）を加工して作成","subitem_description_type":"Other"}]},"item_9_description_5":{"attribute_name":"提供者所属","attribute_value_mlt":[{"subitem_description":"金沢大学医学部","subitem_description_type":"Other"}]},"item_9_identifier_registration":{"attribute_name":"ID登録","attribute_value_mlt":[{"subitem_identifier_reg_text":"10.24517/00067730","subitem_identifier_reg_type":"JaLC"}]},"item_9_relation_28":{"attribute_name":"関連URI","attribute_value_mlt":[{"subitem_relation_name":[{"subitem_relation_name_text":"https://kaken.nii.ac.jp/ja/search/?kw=90026948"}],"subitem_relation_type_id":{"subitem_relation_type_id_text":"https://kaken.nii.ac.jp/ja/search/?kw=90026948","subitem_relation_type_select":"URI"}},{"subitem_relation_name":[{"subitem_relation_name_text":"https://kaken.nii.ac.jp/ja/grant/KAKENHI-PROJECT-62480307/"}],"subitem_relation_type_id":{"subitem_relation_type_id_text":"https://kaken.nii.ac.jp/ja/grant/KAKENHI-PROJECT-62480307/","subitem_relation_type_select":"URI"}},{"subitem_relation_name":[{"subitem_relation_name_text":"https://kaken.nii.ac.jp/ja/report/KAKENHI-PROJECT-62480307/624803071989kenkyu_seika_hokoku_gaiyo/"}],"subitem_relation_type_id":{"subitem_relation_type_id_text":"https://kaken.nii.ac.jp/ja/report/KAKENHI-PROJECT-62480307/624803071989kenkyu_seika_hokoku_gaiyo/","subitem_relation_type_select":"URI"}}]},"item_9_version_type_25":{"attribute_name":"著者版フラグ","attribute_value_mlt":[{"subitem_version_resource":"http://purl.org/coar/version/c_ab4af688f83e57aa","subitem_version_type":"AM"}]},"item_files":{"attribute_name":"ファイル情報","attribute_type":"file","attribute_value_mlt":[{"accessrole":"open_date","date":[{"dateType":"Available","dateValue":"2022-10-31"}],"displaytype":"detail","filename":"ME-PR-YAMASHITA-J-kaken 1993-3p.pdf","filesize":[{"value":"219.7 kB"}],"format":"application/pdf","licensetype":"license_11","mimetype":"application/pdf","url":{"label":"ME-PR-YAMASHITA-J-kaken 1993-3p.pdf","url":"https://kanazawa-u.repo.nii.ac.jp/record/61487/files/ME-PR-YAMASHITA-J-kaken 1993-3p.pdf"},"version_id":"a82410bb-eb07-4638-ad14-496c5d59e5f5"}]},"item_language":{"attribute_name":"言語","attribute_value_mlt":[{"subitem_language":"jpn"}]},"item_resource_type":{"attribute_name":"資源タイプ","attribute_value_mlt":[{"resourcetype":"research report","resourceuri":"http://purl.org/coar/resource_type/c_18ws"}]},"item_title":"遺伝子操作により効果を増強したキラ-T細胞による脳腫瘍に対する養子免疫療法の開発","item_titles":{"attribute_name":"タイトル","attribute_value_mlt":[{"subitem_title":"遺伝子操作により効果を増強したキラ-T細胞による脳腫瘍に対する養子免疫療法の開発"},{"subitem_title":"Adoptive Immunotherapy for Malignant Brain Tumors Using Killer T Lymphocytes Enhanced by Interferon Gamma Gene Transfer","subitem_title_language":"en"}]},"item_type_id":"9","owner":"18","path":["2845"],"pubdate":{"attribute_name":"公開日","attribute_value":"2022-10-31"},"publish_date":"2022-10-31","publish_status":"0","recid":"61487","relation_version_is_last":true,"title":["遺伝子操作により効果を増強したキラ-T細胞による脳腫瘍に対する養子免疫療法の開発"],"weko_creator_id":"18","weko_shared_id":-1},"updated":"2023-07-27T11:53:14.026648+00:00"}