Antibody-directed cytotoxic agents: use of monoclonal antibody to direct the action of toxin A chains to colorectal carcinoma cells.
Antibody-directed cytotoxic agents: use of monoclonal antibody to direct the action of toxin A chains to colorectal carcinoma cells.
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抗体导向的细胞毒剂：使用单克隆抗体引导毒素A链作用于结直肠癌细胞。
DOI：
10.1073/pnas.77.8.4539
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发表时间：
1980
影响因子：
11.1
通讯作者：
Koprowski,H
中科院分区：
文献类型：
--
作者：
Gilliland,DG;Steplewski,Z;Collier,RJ;Mitchell,KF;Chang,TH;Koprowski,H
我们通过将白喉毒素或蓖麻毒素的A链共价偶联到针对结直肠癌肿瘤相关抗原的单抗上，构建了细胞特异性细胞毒抗原。抗体1083-17-1A通过连接3-(2-吡啶二硫)丙酰基或半胱胺基团进行修饰，然后用还原的A链处理，得到保留了抗体部分原有结合特异性的二硫键连接的结合物。结合物对培养的结肠癌细胞显示出细胞毒活性，但在相同浓度范围内对缺乏该抗原的多种细胞株没有毒性。在规定的条件下，几乎100%的带有抗原的培养细胞被杀死，而缺乏抗原的细胞不受影响。含有毒素A链的结合物与单抗偶联，可用于研究各种细胞表面成分的功能，并可能作为肿瘤特异性治疗药物。
We have constructed cell-specific cytotoxic agens by covalently coupling the A chain from diphtheria toxin or ricin toxin to monoclonal antibody directed against a colorectal carcinoma tumor-associated antigen. Antibody 1083-17-1A was modified by attachment of 3-(2-pyridyldithio)propionyl or cystaminyl groups and then treated with reduced A chain to give disulfide-linked conjugates that retained the original binding specificity of the antibody moiety. the conjugates showed cytotoxic activity for colorectal carcinoma cells in culture, but were not toxic in the same concentration range for a variety of cell lines that lacked the antigen. Under defined conditions virtually 100% of antigen-bearing cultured cells were killed, whereas cells that lacked the antigen were not affected. Conjugates containing toxin A chains coupled to monoclonal antibodies may be useful in studying functions of various cell surface components and, possibly, as tumor-specific therapeutic agents.