单克隆抗体3A5-复方中药安迪偶联物的肝癌导向治疗

Effect of monoclonal antibody 3A5 coupled with Chinese medicine compound Andi in targeted treatment of hepatocellular carcinoma

目的:探讨单克隆抗体3A5-复方中药安迪粉针剂偶联物(3A5-Andi)的肝癌导向治疗作用。方法:用单克隆抗体3A5与安迪粉针剂(Andi)制备偶联物,ELISA检测3A5-Andi偶联物保持对人肝癌BEL-7 402细胞的免疫反应性;采用小鼠/裸鼠移植性肿瘤模型,5-FU为阳性对照组,观察12、24和50mg/kg的导向治疗作用。结果:克隆生成法显示,3A5-Andi具有比Andi更强的细胞毒性,二者的IC_(50)分别为2.8 mg/L和5.1 mg/L(P<0.01)。24 mg/kg和50 mg/kg 3A5-Andi ip对小鼠移植性腹水型H_(22)肝癌的生命延长率(LPR)分别为133％和167％(P<0.05);而12mg/kg和24mg/kg Andi的LPR分别为112％和138％(P<0.05)。24 mg/kg 3A5-Andi和12 mg/kg Andi iv对裸鼠移植性人肝癌BEL-7402细胞瘤的瘤重抑制率分别为63.5％和52.2％(P>0.05)。24 mg/kg 3A5-Andi和12 mg/kg Andipt对BEL-7402人肝癌的抑制率分别为75.4％和61.0％(P>0.05)。结论:3A5-Andi偶联物具有一定的肿瘤导向治疗作用;3A5-Andi与Andi比较,3A5-Andi对裸鼠移植人肝癌BEL-7402具有较强的治疗作用;pt方式3A5-Andi比iv疗效更好。

AIM:To explore the anti-tumor effect of monoclonal antibody 3A5 coupled with Chinese medicine compound Andi injection in targeted treatment of hepatocellular carcinoma(HCC). METHODS:Monoclonal antibody 3A5 was used to prepare conjugates with Andi powder. The immunoreactivity of the conjugates on human HCC BEL-7402 cell was detected by ELISA.The targeted therapeutic effects of 12, 24 and 50 mg/kg conjugates were observed in mice/nude mice transplantation tumor models. The positive control group was treated with 5-FU. RESULTS:The detection of clone production indicated that 3A5-Andi has more cytotoxicity than Andi, and their IC_(50) were 2.8mg/L and 5.1mg/L respectively (P<0.01). The survival rates of 24 mg/kg and 50 mg/kg of 3AS-Andi ip on mice transplantation ascites H_(22) HCC were 133% and 167 % respectively (P<0.05), but those of 12 mg/kg and 24 mg/kg of Andi only were 112 % and 138 % respectively (P<0.05). The inhibitory rates of 24mg/kg of 3A5-Andi and 12 mg/kg of Andi ivon nude mice transplantated human HCC BEL-7 402 cell tumor were 63.5 % and 52.5 % respectively (P>0.05). The inhibitory rates of 24mg/kg 3A5-Andi and 12mg/kg Andi pton human HCC BEL-7402 cell were 75.4 % and 61.0 % respectively (P>0.05). CONCLUSION:3A5-Andi conjugates have a tumor targeted therapeutic effect. This effect is stronger than that of Andi only on nude mice transplanted human HCC BEL-7402, and the administration of ptis better than that of iv.