Schechter B, Arnon R, Wilchek M, Schlessinger J, Hurwitz E, Aboud-Pirak E, Sela M
Department of Chemical Immunology, Weizmann Institute of Science, Rehovot, Israel.
Int J Cancer. 1991 May 10;48(2):167-72. doi: 10.1002/ijc.2910480203.
Cis-diamminedichloroplatinum (II) (cis-Pt) complexed to a carboxymethyl dextran-avidin conjugate was targeted to biotin-monoclonal antibody 108 (b-MAb 108). This MAb recognizes the extracellular domain of the epidermal growth factor receptor (EGF-R) on human epidermoid carcinoma (KB) cells over-expressing EGF-R. Cis-Pt-carboxymethyl-dextran-avidin (Pt-dex-Av) containing 60-90 M cis-Pt/M avidin was administered 24 hr following b-MAb108 containing 3-5 M biotin/M MAb. This treatment was potentially more effective in suppressing the growth of established KB tumor xenografts, or in inhibiting the development of lung metastases in nude mice, than free MAb 108, free drug or MAb 108 followed by drug. Replacing b-MAb 108 by unbiotinylated antibody or by b-MAb of a different specificity also yielded lower suppressive effects. The sequential administration of Pt-dex-Av following b-MAb was more effective than introduction of the Pt-dex-Av when already complexed to b-MAb 108. The results presented in this preliminary investigation suggest that Pt-dex-Av is specifically removed from the circulation by b-MAb 108 concentrated at the tumor site.
与羧甲基葡聚糖-抗生物素蛋白缀合物络合的顺二氯二氨铂（II）（顺铂）靶向生物素化单克隆抗体108（b-MAb 108）。该单克隆抗体识别过表达表皮生长因子受体（EGF-R）的人表皮样癌（KB）细胞上表皮生长因子受体的细胞外结构域。在含有3-5 M生物素/M单克隆抗体的b-MAb108给药24小时后，给予含有60-90 M顺铂/M抗生物素蛋白的顺铂-羧甲基葡聚糖-抗生物素蛋白（Pt-dex-Av）。这种治疗在抑制已建立的KB肿瘤异种移植物生长或抑制裸鼠肺转移发展方面可能比游离的单克隆抗体108、游离药物或先给予单克隆抗体108后给予药物更有效。用未生物素化的抗体或不同特异性的b-MAb替代b-MAb 108也会产生较低的抑制效果。在b-MAb之后序贯给予Pt-dex-Av比将Pt-dex-Av与b-MAb 108预先络合后再引入更有效。这项初步研究的结果表明，Pt-dex-Av在肿瘤部位被b-MAb 108集中从循环中特异性清除。
