Nakamura K, Kubo A, Hashimoto S
Department of Radiology School of Medicine, Keio University, Tokyo, Japan.
Hybridoma. 1990 Aug;9(4):351-62. doi: 10.1089/hyb.1990.9.351.
The potential effects of free circulating antigen on the ability of monoclonal antibodies to target tumors in vivo were investigated. Tumor models consisted of HCC, NuE and PLC cell lines producing AFP xenografted in nude mice, and the NuE-treated mouse designated as the NuE-bearing mouse injected with AFP prior to the administration of antibody. Immunoscintigraphy and biodistribution were evaluated by using 125I-labeled monoclonal antibody 19F12 raised against AFP. Gel chromatography analysis of plasma from the PLC-bearing mouse which excreted 400 ng AFP/ml in blood injected with 125I-19F12 indicated that all injected antibody 19F12 formed an immune complex in plasma. No immune complex was present in plasma from the NuE-bearing mice, where blood AFP levels were 7 ng/ml, while the intact antibody was found to remain partly in plasma from the NuE-treated mouse. Radioactivities in the whole body of NuE-bearing and NuE-treated mice eventually cleared at the same rate. Our experimental results indicated that the endogeneous circulating antigen retained the antibody in the whole body for a longer period. The ability of monoclonal antibodies to target tumors was influenced not only by how much antigen was present but also by how rapid the antigen was cleared in the blood.
研究了游离循环抗原对单克隆抗体在体内靶向肿瘤能力的潜在影响。肿瘤模型由接种于裸鼠体内的产生甲胎蛋白的肝癌、NuE和PLC细胞系组成，在注射抗体前，将注射了甲胎蛋白的经NuE处理的小鼠指定为携带NuE的小鼠。通过使用针对甲胎蛋白产生的125I标记单克隆抗体19F12评估免疫闪烁显像和生物分布。对在血液中排泄400 ng甲胎蛋白/毫升并注射了125I-19F12的携带PLC的小鼠的血浆进行凝胶色谱分析表明，所有注射的抗体19F12在血浆中形成免疫复合物。在携带NuE的小鼠血浆中不存在免疫复合物，其血液甲胎蛋白水平为7 ng/毫升，而发现完整抗体部分保留在经NuE处理的小鼠血浆中。携带NuE的小鼠和经NuE处理的小鼠全身的放射性最终以相同速率清除。我们的实验结果表明，内源性循环抗原使抗体在全身保留更长时间。单克隆抗体靶向肿瘤的能力不仅受抗原存在量的影响，还受血液中抗原清除速度的影响。
