MG系列胃癌单克隆抗体的内化研究

INTERNALIZATION OF RADIOLABELED MG SERIES MONOCLONAL ANTIBODIES AGAINST HUMAN GASTRIC CANCER

单克隆抗体在肿瘤细胞中的调变会极大地影响其在临床应用中的治疗效果。本研究用^(125)I标MG系列单抗与胃癌细胞系孵育,等渗酸性缓冲液处理,观察本室MGC_1,MGD_1,MG_7MG_5,和MGb_2抗体的内化特点。结果如下:MGC_1,MGD_1,和MG_7很快进入靶细胞KATOⅣ内,150分钟内化程度>50％:MG_5仅27.4％进入KATOⅣ内;进入靶细胞SGC-7901的MGb_2抗体只有9.55％;内化抗体的代谢方式也不同;MGC_1在37℃时呈进行性降解;MGd_1在37℃先是很快降解,然后进入平台期,而MGb_2内化较少,其降解也不同手前两者。提示用于导向治疗时应根据抗体的特点选择合适的“杀伤弹头”及交联方法。

Modulation of MoAbs by specific tumor cells may. have great influence on the efficacy of MoAb therapy in clinical trials, Anti-human gastric cancer MoAbs, MGcl, MGdl, MG5, MG7, MGb2 were labeled with 125-iodine and allowed to bind to cultured live cells (SGC-7901, KATOIII) at 4℃ and 37℃. Radionuclide internalization was determined by the amount of radioactivity in the cell pellets after acid trecatment The study showed that more than 50% of MGcl, MGdl, MG7 could be rapidly internalized into KA-TOIII cells at 4℃ and 37℃ in 150 min; While 27.4% of MG5 into KATOIII and only 9.55% of MGb2 into SGC-7901 at 37℃. We also observed that the internalized MoAbs catabolized differently. MGcl progressively catabolized at 37℃while MGdlcatabolized rapidly at first, and slowly afterwards. The mode of internalized MGb2 was .different from the above ones. Therefore in targeting therapy we should choose apropiriate 'killing ammunitions' and modes of conjugating according to different antibodies.