摘要
本文报道天花粉蛋白(TCS)为弹头药物经 SPDP 法与抗 CEA 单抗连接制备成免疫偶联物即免疫毒素,通过凝胶过滤和离子梯度层析纯化后,仍保留特并识别靶细胞抗原的免疫活性。体外毒性试验证实免疫毒素具有杀伤肿瘤细胞作用,它比 TCS 和正常小鼠 Ig 与 TCS 偶联物对 IOVO 细胞的毒性作用(I.C.50)分别增强150和2000倍左右。对不同肿瘤细胞 CEA 含量分析,发现这一作用与肿瘤细胞表面 CEA 含量成正比.体内实验结果同样表明,免疫毒素对潜伏期和生长期的人结肠癌裸鼠移植瘤有明显的抑瘤作用,其抑瘤率分别为76—80%和68—72%,并能延长荷瘤裸鼠生存时间,而对于宿生来出现明显的毒付作用.
Triehosanthin(TCS),a ribosome—inactivation protein,was conjugated with B_3IgG,an anti—CEA monoclonal antibody which had been cross—linked with SPDP,to form an immunotoxin TCS—B_3IgG via a disulfide bond.The immunotoxin had been purified by Sephadex G—150 gel filtration and Blue Sepharose—4B gradient ion exehange chromatograph.It has been that IgG potion of the immunotoxin molecules retained the ability to form complexs with CEA after eon-jugate to TCS.The vitro cytotoxicity of the immunotoxin to human colonic carcinoma(LoVo)cell lines was approximately 150—fold higher than that of free TCS or 2000—fold higher that of the conjugate of TCS with normal mouse IgG(TCS—NmIgG).Moreover,a parallel relation-ship was observed between the killing intensity with the immunotoxin and the CEA content de-tected on surfaces and lysates of diferent target tumor cell lines.Results of our preliminary in vivo with the immunotoxin on inhibition of tumor growth and incubation period of human colonic eareinoma xenografts in made mice were also encouraging.Without obvious toxic effect to host mice,the inhibition rate of the carcinoma reached 68—73% and 76—80%,and immunotoxin prolonged the life of animals bearing human colonic carcinoma.The above experiments dealing with immunotherapy of human colonic carcinoma with our TCS —B_3IgG immunotoxin showed promise in clinic application.
出处
《中国免疫学杂志》
CAS
CSCD
北大核心
1992年第5期300-303,共4页
Chinese Journal of Immunology
