Ota Y, Oehr P, Inaba N, Takamizawa H
Department of Obstetrics and Gynecology, Faculty of Medicine, University of Chiba, Japan.
Asia Oceania J Obstet Gynaecol. 1993 Dec;19(4):449-57. doi: 10.1111/j.1447-0756.1993.tb00406.x.
Anti-tumor effects of the following 2 cis-diammin (1, 1-cyclobutandicarboxylato) platin II (carboplatin, Bristol-Myers-Squibb) conjugates were evaluated through both in vitro and in vivo experiments: (1) carboplatin coupled with anti-cytokeratin monoclonal antibody (MAb), TS1 via carboxymethyl dextran (carboplatin-carboxymethyl dextran-TS1), and (2) carboplatin-carboxymethyl dextran-avidin targeted to biotinylated TS1. Using 1-ethyl-3(3-dimethylaminopropyl)-carbodiimide and N-hydroxysuccinimide, carboplatin was conjugated to carboxymethyl dextran, TS1, or avidin, at high molar ratios. The staining positivity of carboplatin-carboxymethyl dextran-TS1 in indirect immunofluorescence was almost identical to that of the original MAb. The average dose of carboplatin given in each treatment was about 60% of a clinical dose. Regarding cytotoxicity, the free drug showed the strongest effect and the best dose-dependency in cell lines: HeLa and ZR-75-1. An in vivo study giving carboplatin-MAb conjugates or free drug to HeLa tumor bearing nude rats proved that the efficacy of carboplatin-carboxymethyl dextran-TS1 in HeLa tumor was not greater than that of the free carboplatin.
通过体外和体内实验评估了以下两种顺式二氨（1,1 - 环丁烷二甲酸根）铂II（卡铂，百时美施贵宝公司）偶联物的抗肿瘤作用：（1）卡铂通过羧甲基葡聚糖与抗细胞角蛋白单克隆抗体（MAb）TS1偶联（卡铂 - 羧甲基葡聚糖 - TS1），以及（2）靶向生物素化TS1的卡铂 - 羧甲基葡聚糖 - 抗生物素蛋白。使用1 - 乙基 - 3（3 - 二甲基氨基丙基） - 碳二亚胺和N - 羟基琥珀酰亚胺，以高摩尔比将卡铂与羧甲基葡聚糖、TS1或抗生物素蛋白偶联。卡铂 - 羧甲基葡聚糖 - TS1在间接免疫荧光中的染色阳性率与原始单克隆抗体几乎相同。每次治疗中给予的卡铂平均剂量约为临床剂量的60％。关于细胞毒性，游离药物在细胞系HeLa和ZR - 75 - 1中显示出最强的作用和最佳的剂量依赖性。一项对携带HeLa肿瘤的裸鼠给予卡铂 - 单克隆抗体偶联物或游离药物的体内研究证明，卡铂 - 羧甲基葡聚糖 - TS1在HeLa肿瘤中的疗效不大于游离卡铂。
