半乳糖基抗CD_3单抗的制备及体内趋肝性研究

The Preparation and Study on Hepatic Targeting Tendency of Galactosyl anti CD 3 McAb in Mice

目的 了解半乳糖基抗 CD3 单抗 - TIL 复合物 (Gal- Anti- CD3 - Mc Ab- TIL)的体内趋肝细胞性。方法 制备半乳糖基抗 CD3 单抗 (Gal- Anti- CD3 - Mc Ab) ,采用苯酚 -硫酸法测其糖密度 ;经动物外周静脉分别注入用 1 2 5 I标记的抗 CD3 单抗 (Anti- CD3 - Mc Ab)和用 1 3 1 I标记的 Gal- Anti- CD3 - Mc Ab,分别测定两者在动物体内各脏器的放射活性。结果 Gal- Anti- CD3 - Mc Ab的糖密度值为 5 8.12 ;外周静脉注射给药 ,Anti- CD3 - Mc Ab趋于肺内浓聚 ,而 Gal- Anti- CD3 - Mc Ab有显著的趋肝性 ,且于靶器官有较长时间停留。结论 经外周静脉途径注射 ,Gal- Anti-CD3 - Mc Ab有显著的体内趋肝细胞性 ,其中半乳糖基与肝结合蛋白所介导的受体 -配体反应在 Gal- Anti- CD3 - Mc

Objective This study sought to reduce the recurrence rate of primary liver cacer (PLC) after hepatectomy by increasing the concentration of infiltrating lymphocytes(TILs) at the target organ. Methods It has been reported that galactosyl anti CD 3 McAb has an obvious hepatic targeting tendency in vitro. On the basis of that work, the present authors conducted a study in mice. Galactosyl anti CD 3 McAb was prepared and its carbohydrate density was measured with the phenol sulphyric acid method, and then anti CD 3 McAb (labeled with 125 I) and galactosyl anti CD 3 McAb (labeled with 131 I) were infused respectively via the peripheral vein and the radioactivity in each organ was measured. Results The carbohydrate density of galactosyl anti CD 3 McAb in this experiment was 58.12, which effectively guaranteed the specific binding between galactosyl anti CD 3 McAb and hepatic binding protein(HBP). It was also noticed that anti CD 3 McAb tended to aggregate in the lungs while being infused via the peripheral vein, and that galactosyl anti CD 3 McAb had an obvious hepatic targeting tendency in vivo and it stayed in liver for quite a long period.Conclusions Galactosyl anti CD 3 McAb has an obvious hepatic targeting tendency in vivo while being infused through peripheral vein; this may be due to the specific binding between galactose and HBP.