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Boron10・モノクローナル抗体による癌の選択的原子炉療法の研究

使用Boron10单克隆抗体进行癌症选择性核治疗的研究

基本信息

批准号：
60010052
负责人：
三島豊
金额：
$ 4.48万
依托单位：
Kobe University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Cancer Research
财政年份：
1985
资助国家：
日本
起止时间：
1985 至无数据
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-60010052/
关键词：
単クローン抗体熱中性子捕捉療法原子炉療法

项目摘要

本研究の特色は癌細胞表面にある多種の抗原エピトープに夫々特異結合する多種類の単クローン抗体(MoAb)を作成し、此れをcarrierとする【^(10)B】・MoAbを合成・投与し熱中性子捕捉療法を行う点にある。単独でも有効であるが、今迄開発して来た代謝活性利用の方法(例えばp-borono-phenylalanine(BPA)をcarrierとする【^(10)B_1】-BPA・HClによる黒色腫治療)を併用すれば相加・相乗効果が期待できる。本年度業績も両者に跨っている。【◯!1】(1)ヒト型抗体を安定産生するヒト・マウスヘテロハイブリドーマを肺癌をモデル実験として作成(2)ヒト腫瘍と反応するマウス単クローン抗体産生ハイブリドーマから単離したマウス【V】遺伝子にヒトFc遺伝子を接続、得られた接合遺伝子をマウス骨髄腫に導入、分泌型キメラ抗体を産生させた。結合活性精査中(3)ラットより得た抗黒色腫抗体35種の抗原認識能解析【◯!2】(1)【^(10)B】含量の高い化合物M・【^(10)B_(12)】【H_(11)】【NH_3】の【H_3】を一旦【Na_3】に変換後、【Cl_2】C=Sで処理してM・【^(10)B_(12)】【H_(11)】NX=C=Sを得た。期待に反しアミノ基、水酸基と反応せず、抗体への【^(10)B】導入剤として不適(2)【M_2】【^(10)B_(12)】【H_(11)】SHのMBS処理で【^(10)B】導入剤を合成する試みも二重結合へのSH付加が起らず不成功(3)M・【^(10)B_(12)】【H_(11)】【NH_2】【CH_2】COOH,M・【^(10)B_(12)】【H_(11)】【NH_2】CO【CH_2】【CH_2】COOHの合成を企画中【◯!3】【^(10)B_1】-BPA・HClの摘出心臓,血管,腸管に対する作用を収縮性を指標とし測定。作用は類似構造の化合物phenylalanineとL-dopaの中間にあり、濃度【10^(-4)】M以下では微腰で検出不能。既報のマウス急性毒性試験と共に本薬物の安全性を示唆。ラット試験は次年度へ繰り越し【◯!4】【^(10)B_1】-BPA・HCl15.8g(液量1.7l)を体重79Kgの黒色腫患豚に4.6時間連続して静脈内注入し、投与開始後1.75〜5.25時間の間中性子照射。投与終亨1時間後採取の腫瘍と血液中のB濃度は夫々6〜11と2.4μg/g湿重量と好成績、観察続行中の治癒状況も良好である。然し従来の病巣周辺皮下・筋肉内投与例と異り完溶透明薬液を作る必要上酸性大となり、ヒト患者への適用性は更に検討中。

This study is characterized by the preparation of multiple types of single antibody (MoAb) that bind specifically to multiple antigens on the surface of cancer cells, and the synthesis, administration, and application of MoAb to capture therapy. There have been some unique approaches to metabolic activity utilization (e.g., p-borono-phenylalanine(BPA) carrier and BPA·HCl treatment for black tumors), which have been developed to date. This year's performance is very important.【◯! 1) Production of stable anti-tumor antibodies (2) Production of stable anti-tumor antibodies (3) Production of stable anti-tumor antibodies (4) Production of stable anti-tumor antibodies (5) Production of stable anti-tumor antibodies (6) Production of stable anti-tumor antibodies (7) Production of stable anti-tumor antibodies (8) Production of stable anti-tumor antibodies (9) Production of stable anti-tumor antibodies ( 35 kinds of antigen recognition ability analysis of anti-melanoma antibody in binding activity analysis (3) 2)(1)[^(10)B] content of high middle compounds M·[^(10)B_(12)][H_(11)][NH_3] and [H_3] once [Na_3] is changed,[Cl_2] C=S is treated and M·[^(10)B_(12)][H_(11)] NX=C=S is obtained. Antibodies and antibodies [^(10)B] were introduced into MBS treatment of [^(10)B],[^(10)B_(12)],[H_(11)] SH, and [^(10)B] were introduced into MBS treatment. M·[^(10)B_(12)][H_(11)][NH_2] CO [CH_2][CH_2] COOH synthesis is planned 3. Determination of contractile index of BPA·HCl on heart, blood vessels and intestine. The effect of phenylalanine is similar to that of L-dopa, and the concentration of L-dopa is lower than [10^(-4)]. The acute toxicity test has been reported and the safety of this drug has been demonstrated. The next year's 4][^(10)B_1]-BPA·HCl 15.8g (1.7l) was injected intravenously into a black dolphin weighing 79Kg for 4.6 hours continuously, and the intermittent sub-irradiation was performed for 1.75 - 5.25 hours after the start of administration. After 1 hour of administration, B concentration in the blood was 6 ~ 11 μg/g wet weight. Good results were obtained. Good healing condition was observed. However, in the future, the application of subcutaneous and muscle injection in the peripheral part of the disease should be discussed in detail.