Kitamura K, Takahashi T, Yamaguchi T, Kitai S, Amagai T, Imanishi J
Department of Surgery, Kyoto Prefectural University of Medicine.
Jpn J Clin Oncol. 1990 Jun;20(2):139-44. doi: 10.1093/oxfordjournals.jjco.a039378.
The monoclonal antibody A7 (MoAb A7), which belongs to IgG1, was digested with pepsin to yield F(ab')2 fragments. The maximum binding to the human colon cancer cell line, SW1116, was 27% with 125-I labeled whole MoAb A7 and 24% with 125-I labeled F(ab')2 fragments using an in vitro binding assay. The results showed that the binding activity of F(ab')2 to SW1116 was practically the same as that of whole MoAb A7. The preferred localization of the fragments to tumor tissue, compared with normal mouse tissue, was demonstrated in mice carrying SW1116 xenografts. The tumor:blood ratio three days after injection was 2.64:18.5 for whole MoAb A7:F(ab')2, respectively. The tissue:blood ratios for the F(ab')2 fragments showed a value of 18.5 in tumors, whereas its was a value less than 1.0 in normal organs. The tumor accumulation of F(ab')2 fragments was also dependent on the antigenic expression of each tumor among xenografts of colon carcinoma SW1116 and WiDr, and squamous cell carcinoma KB. In kinetic experiments with whole MoAb A7 and its F(ab')2 fragments, whole MoAb A7 was lost, with a half-life of 4 days, in both blood and tumors, whereas F(ab')2 fragments were rapidly lost with a half-life of 1.5 days. These results suggested that the F(ab')2 fragments were cleared from the blood faster than was whole MoAb A7.
单克隆抗体A7（MoAb A7）属于IgG1，用胃蛋白酶消化后产生F(ab')2片段。使用体外结合试验，125-I标记的完整MoAb A7与人类结肠癌细胞系SW1116的最大结合率为27%，125-I标记的F(ab')2片段与SW1116的最大结合率为24%。结果表明，F(ab')2与SW1116的结合活性与完整MoAb A7的实际相同。在携带SW1116异种移植物的小鼠中，与正常小鼠组织相比，这些片段在肿瘤组织中的优先定位得到了证实。注射后三天，完整MoAb A7与F(ab')2的肿瘤与血液之比分别为2.64:18.5。F(ab')2片段的组织与血液之比在肿瘤中显示为18.5，而在正常器官中则小于1.0。F(ab')2片段在肿瘤中的积累也取决于结肠癌SW1116和WiDr异种移植物以及鳞状细胞癌KB中每个肿瘤的抗原表达。在完整MoAb A7及其F(ab')2片段的动力学实验中，完整MoAb A7在血液和肿瘤中均以4天的半衰期消失，而F(ab')2片段以1.5天的半衰期迅速消失。这些结果表明，F(ab')2片段从血液中清除的速度比完整MoAb A7更快。
