胃癌单克隆抗体偶合物导向化疗的实验研究

Experimental studies on the targeting chemotherapy of human gastric cancer with monoclonal antibody conjugated with Pingyangmycin

将制备的鼠抗人胃癌单克隆抗体（8711C1McAb）纯化后，以Iodogen法标记125I，Manabe法偶联平阳霉素。间接免疫荧光试验和3H-TdR掺入法（抑制率81．5％）证明标记物免疫活性保持良好。5只人胃癌大鼠模型尾静脉注射125I-McAb，放射免疫自显影有4只移植瘤体外显像（80％），T／NT值为3．12，显著高于对照组（P＜0．01）。PPM导向治疗动物试验，4只荷瘤大鼠注射PPM5次，肿瘤抑制率为58．2％，与对照组差异有显著性（P＜0．05）；组织学检查证实肿瘤组织出现弥漫性病理改变．癌细胞核固缩、溶解。结果证明PPM对胃癌细胞有较强的导向杀伤作用。

The murine monoclonal antibody against human gastric cancer (8711C1 McAb) was purified, and labeled with 125I(125I-McAb)by Iodogen method and conjugated with PPM by Manabe's method. The immunoactivity of 125I-McAb was demostrated by indirect immunofluorescence technique and the cytotoxic effect to target cells of PPM was illustrated by 3H-TdR method(ihhibition rate of 81.5% to gastric cancer cell growth). In radioimmunoimaging test, 4 of 5 rats bearing human gastric cancer showed positive images after injection of 125I-McAb, and with an average T/NT value of 3.12 which was significantly higher than that of control groups(P<0. 01). A tumor growth inhibition rate of 58. 2% was observed in 4 rats bearing human gastric cancer after injection of PPM for 5 times, and was significantly higher than that in the control group(P<0. 05). The marked morphological changes including nuclei degeneration and necrosis of tumor cells were observed in tumor tissues in pathological examination.