一种由抗TF抗原的McAb和Daunomycin构建的免疫霉素在体外对人癌细胞的杀伤作用

Selective Cytocidal Effect in Vitro on Human Carcinoma Cell Lines of an Immunotoxin Composed of Daunomycin and a Monoclonal Antibody to TF Antigen

在纯化了的抗TF(Thomsen—Friedenreich)抗原的McAb49H.8和抗肿瘤药物道诺霉素(Daunomyciu,DM)之间通过酸性敏感的顺式乌头酰基(Cis—Aconityl,CA)配接成免疫毒素49H.8—CA—DM.通过DNA合成抑制检测了此配接物在3个人癌细胞株(647V,EJ—S—47, LOVO)和一种小鼠肺癌细胞株KLN205的体外抗肿瘤效应.此免疫毒素显示了有相对选择性的细胞杀伤作用,对49H.8抗原强阳性的胱膀癌细胞株647V有确定的细胞杀伤效应,且呈剂量依赖性的,而在同一剂量范围对细胞表面缺乏49H.8抗原的小鼠肺癌细胞株KLH205不显示细胞毒性作用,对49H.8抗原弱阳性的细胞株EJ—S—47和LOVO的作用是不恒定的.

We have conjugated an immunotoxiu 49H.8-CA-DM by iutroduciug of an acid-sensitive cis-aconityl(CA) linkage between the antitumor drug dauno-mycin(DM) and a purified anti-TF antigea McAb (49H.8) .Antitumor tests in vitro of the conjugate by inhibition of DNA synthesis were performed in 3 human carcinoma lines (647V, EJ-S-47, LOVO) and a murine carcinoma line KLN205.The conjugated 49H.8-CA-DM showed relatively selective cytocidal activity in vitro on the human carcinoma cell lines, certainly on the strong 49H.8-anigen-positive bladder cancer cell line 647Vand such cytotoxic effect was dependent on the dosage of the immunotoxin, but in the same dose range it was not cytotoxic to the murine lung cancer cell line KLN205 lacking 49H.8 antigea,and did not show constant effect on the weak 49H.8 antigen positive lines EJ-S-47 and LOVO.