Gilliland D G, Steplewski Z, Collier R J, Mitchell K F, Chang T H, Koprowski H
Proc Natl Acad Sci U S A. 1980 Aug;77(8):4539-43. doi: 10.1073/pnas.77.8.4539.
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.
我们通过将白喉毒素或蓖麻毒素的A链与针对结肠直肠癌肿瘤相关抗原的单克隆抗体共价偶联，构建了细胞特异性细胞毒性制剂。抗体1083 - 17 - 1A通过连接3 -（2 - 吡啶二硫基）丙酰基或胱胺基进行修饰，然后用还原型A链处理，得到保留抗体部分原始结合特异性的二硫键连接的缀合物。这些缀合物对培养中的结肠直肠癌细胞显示出细胞毒性活性，但在相同浓度范围内对缺乏该抗原的多种细胞系无毒。在特定条件下，几乎100%携带抗原的培养细胞被杀死，而缺乏该抗原的细胞则不受影响。含有与单克隆抗体偶联的毒素A链的缀合物可能有助于研究各种细胞表面成分的功能，并有可能作为肿瘤特异性治疗剂。
