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アイソトープ標識モノクローナル抗体A7による大腸癌放射免疫療法の臨床応用
https://doi.org/10.24517/00063464
https://doi.org/10.24517/0006346464621fde-b22d-4431-8330-fa1e682c9f65
名前 / ファイル | ライセンス | アクション |
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ME-PR-TONAMI-N-kaken 2006-2p.pdf (103.4 kB)
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Item type | 報告書 / Research Paper(1) | |||||
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公開日 | 2021-11-05 | |||||
タイトル | ||||||
タイトル | アイソトープ標識モノクローナル抗体A7による大腸癌放射免疫療法の臨床応用 | |||||
タイトル | ||||||
言語 | en | |||||
タイトル | Application of Radiolabeled Monoclonal A7 Antibody for Radioimmunotherapy of Human Colon Cancer | |||||
言語 | ||||||
言語 | jpn | |||||
資源タイプ | ||||||
資源タイプ識別子 | http://purl.org/coar/resource_type/c_18ws | |||||
資源タイプ | research report | |||||
ID登録 | ||||||
ID登録 | 10.24517/00063464 | |||||
ID登録タイプ | JaLC | |||||
著者別表示 |
Tonami, Norihisa
× Tonami, Norihisa |
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提供者所属 | ||||||
内容記述タイプ | Other | |||||
内容記述 | 金沢大学医学系研究科 | |||||
書誌情報 |
平成16(2004)年度 科学研究費補助金 基盤研究(B) 研究成果報告書概要 en : 2004 Fiscal Year Final Research Report Summary 巻 2001 – 2004, p. 2p., 発行日 2006-07-10 |
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抄録 | ||||||
内容記述タイプ | Abstract | |||||
内容記述 | アイソトープ標識技術を応用して,固形癌の内部照射ターゲティング療法の臨床応用を目標とする.アイソトープで標識されたモノクローナル抗体を体内に投与すれば,がん抗原発現部位のがん組織に特異的に集積する.造血器悪性腫瘍をターゲットとした研究では,放射線感受性や腫瘍組織へのアクセスなど固形癌よりも有利な点が多いため成績が良い.研究代表者の施設でも抗CD20モノクローナル抗体を治療用β線放出アイソトープであるY-90で標識したアイソトープ抗癌剤の臨床試験が進行中である.一方,固形癌を対象とした臨床研究では,進行期で腫瘍体積も大きな症例が多く,放射免疫療法にとって原理的に不利である.本研究では,治療用放射性アイソトープ標識方法を最適化し,最終的には固形癌に対する放射免疫療法の治療効果を臨床的に評価する. 抗大腸腺癌モノクローナル抗体A7と治療用β線放出アイソトープのI-131および体内動態観察用のIn-111での標識方法をまず第1にin vitroで検討した.I-131標識モノクローナル抗体A7およびIn-111標識体もそれぞれ37MBq/mg以上の比放射能での標識が可能であった.さらに,新しい治療用アイソトープであるRe-186での標識も行い,十分な比放射能が達成できた.一方,標識後の免疫活性をLindomoアッセイで評価した.それぞれの免疫活性分画(immunoreadtive fraction)は,I-131標識抗体が74%であり,In-111標識抗体は83%,Re-186標識抗体は67%と免疫活性は標識後も十分保持された.引き続きヒト大腸癌LS180移植ヌードマウスモデルに投与して,体内動態,抗腫瘍効果,毒性の評価を行った.In vivoイメージングでは,腫瘍に一致したアイソトープ標識抗体の集積が確認された.さらに,治療実験を担癌マウスで行った.その結果,特異的抗体を投与したマウスでは,投与量依存的に腫瘍の増殖抑制効果が認められた.より小さな病変に対する治療効果を検討するために,腹膜播種モデルを作成し,I-131標識抗体とRe-186標識抗体A7を投与した.Re-186標識抗体の方がI-131標識抗体よりも1.6倍腫瘍への吸収線量が増加することが判明し,Re-186標識抗体の内照射治療における有用性が示された. |
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抄録 | ||||||
内容記述タイプ | Abstract | |||||
内容記述 | Using monoclonal antibody specific for tumor associated antigen expressed on human malignant tumor cells, therapeutic radionuclides can be delivered to the tumor lesion in vivo. For this approach, the stable radiometal chelates is required. Re-186 or Re-188 are expected to be the choice of radionuclide for radioimmunotherapy. We have assessed the conjugation procedure of the MAG3 chelate and HYNIC chelate. The stability of the radiolabel was found to be satisfactory. A monoclonal antibody A7 was used for the project. This antibody recognizes adenocarcinoma related antigen on the variety of human colon cancer cells. The A7 antibody was labeled with Re-186, resulting in the specific activity of greater than 37 MBq/mg. And the immunoreactivity of the labeled antibody was 67%, which is equivalent for that of I-131 labeled counterpart. LS180 human colon cancer cells were inoculated to the Balb/c nude mice. In vivo imaging with either I-131 or Re-186 labeled A7 provided well-delineated tumor. Therapy trial study demonstrated that Re-186 A7 delivered 1.6 times higher radiation to the tumor than I-131 A7. Thus, Re-186 antibody should be the attractive modality for radioimmunotherapy. We have tried to increase the tumor uptake of radiolabeled antibodies by modifying the delivery system to the tumor tissue. The combination usage of angiotensin-II and a kininase inhibitor, enalapril maleate, increased the mouse blood pressure from 95/61 to 153/67. And the tumor uptake was also increased by the factor of 1.62 with little change in normal organ distribution. In conclusions, enhanced tumor uptake was achieved by manipulating hemodynamics and vascular permeability of the tumor tissue and this technique can be applied for effective targeting. |
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内容記述 | ||||||
内容記述タイプ | Other | |||||
内容記述 | 研究課題/領域番号:13470180, 研究期間(年度):2001 – 2004 | |||||
内容記述 | ||||||
内容記述タイプ | Other | |||||
内容記述 | 出典:「アイソトープ標識モノクローナル抗体A7による大腸癌放射免疫療法の臨床応用」研究成果報告書 課題番号13470180 (KAKEN:科学研究費助成事業データベース(国立情報学研究所)) (https://kaken.nii.ac.jp/ja/report/KAKENHI-PROJECT-13470180/134701802004kenkyu_seika_hokoku_gaiyo/)を加工して作成 |
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著者版フラグ | ||||||
出版タイプ | AM | |||||
出版タイプResource | http://purl.org/coar/version/c_ab4af688f83e57aa | |||||
関連URI | ||||||
識別子タイプ | URI | |||||
関連識別子 | https://kaken.nii.ac.jp/ja/search/?kw=60019940 | |||||
関連名称 | https://kaken.nii.ac.jp/ja/search/?kw=60019940 | |||||
関連URI | ||||||
識別子タイプ | URI | |||||
関連識別子 | https://kaken.nii.ac.jp/ja/grant/KAKENHI-PROJECT-13470180/ | |||||
関連名称 | https://kaken.nii.ac.jp/ja/grant/KAKENHI-PROJECT-13470180/ | |||||
関連URI | ||||||
識別子タイプ | URI | |||||
関連識別子 | https://kaken.nii.ac.jp/ja/report/KAKENHI-PROJECT-13470180/134701802004kenkyu_seika_hokoku_gaiyo/ | |||||
関連名称 | https://kaken.nii.ac.jp/ja/report/KAKENHI-PROJECT-13470180/134701802004kenkyu_seika_hokoku_gaiyo/ |