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单链免疫毒素的体外细胞毒性质及体内抗肿瘤活性的研究

Immunotoxins composed of monoclonal antihuman T Iymphocyte antibody and single chain ribosome—inactivating proteins:antitumor effects in vitro and in Vivo
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摘要 运用异型双功能交联剂2—亚氨基四氢噻吩将抗人 T 淋巴细胞单克隆抗体 H65(CD5)与单链核糖体失活蛋白苦瓜毒素2及玉竹毒素2偶联后形成的免疫毒素分别称之为 H65—MOR2及 H65—PGN2.体外实验表明上述两种免疫毒素对靶细胞 Molt—4及正常人周血 T 淋巴细胞具有明显的特异性细胞毒作用,而对骨髓中的造血祖细胞没有影响。Balb/c 裸鼠皮下注射 Molt—4细胞,待长出实体瘤以后,腹腔注射免疫毒素 H65—MOR2或 H65—PGN2U10μ(?)/只/48小时可以特异性地抑制肿瘤的生长.实验结果表明这类免疫毒素可以用于体内治疗肿瘤转移灶、某些自身免疫性疾病以及在异体骨髓移植中清除引起移植物抗宿主病(GVHD)的 T 细胞. Two new single chain ribosome—inactivating proteins,polygonin2 from the roots of Polygonatum odoratum and momordin2,from the seeds of Momordica charantia,inhinited pro- teib synthesis potentially in rabbit reticulocyte lysate,but were relatively low toxic to Molt—4 cells.polygonin2 and momordin2 were conjugated to H65 monoclonal antibody that recognized human T lymphocyte CD5 surface antigen using a heterobifunctional crosslinking reagent 2— iminothiolane.The resulting immunotoxins,referred to as H65—PGN2 and H65—MOR2, showed potent specific cytotoxicity to target cell Molt—4 and human peripheral blood T lympho- cyte,but had no effect on human hematopoietic cells.Injection of Molt—4 cells s.c.into Balb/c nu/nu mice developed into a solid tumor.Administration of the H65—PGN2 or H65—MOR2 immunotoxins i.p.10 ug per mice at 48—h intervals suppressed tumor growth specifically.The resulting showed that clinical studied were warranted to use these conjugates for the therapy of autoimmune diseases as well as the ex vivo purging of T lymphocyte in ABMT.
出处 《中国免疫学杂志》 CAS CSCD 北大核心 1992年第6期356-360,共5页 Chinese Journal of Immunology
关键词 免疫毒素 单克隆抗体 肿瘤免疫学 Immunotoxin Ribosome—inactivating protein monoclonal antibody
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