The Animal Experimental Studies On The Radioimmunotherapy Of The Hepatoma With ～(131)Ⅰ-human Anti-HBsAg Fab

We prepared successfiuly the human anti-HBsAg Fab by genetic engineering technology.The purpose of this study was to explore the possibility of anti-HBsAg Fab as a carrier of HCC radioimmunotheray and the influence on the therapeutic efficacy and radiotoxicity by different routes of administration. Methods the human anti-HBsAg Fab and S102,the murine McAb to HbsAg,were radioiodinated with iodine-13 I using iodogen method The hepatoblastoma cell line HepG2.2. 15 transfected with cloned HBV DNA as the targetMTT method was used to evalute the injury rate of I-anti- HbsAgFab. The nude mice model with human hepatoma HepG2.2.15 were injected with 11-anti-HBsAgFab intratumoral(IT) and into the peritoneal cavity([P), and 131I-S102 and 131I-nFab were used as controls. Radioimmunoimage was taken on different intervals after injection of the labelled antibodies to the nude mice, and tissue distribution was measured. The tumor growth inhibition rate was determined by measurement of tumor volume.The radiotoxicity was evaluted by leukocyte and platelet counts monitored at weekly intervals; Results (I) 11-anti-I-LBsAgFab had a strong cytotoxic effect to HepG2.2.15,as strong as the 1311-S102 and the sustained 1311 control group.(2) The 131I-anti-HBsAgFab-IP group developed tumor positive images after 24h of intlision,and 131I-S,02 needed 72h. (3) The percentage of the injected dose/gram tissue (%LD/g) of 131L-anti-HBsAgFab in tumor in the IT group was over 3 fold higher than that of the IPgroup and over 7 fold higher than that of 131L-nFab-IT control group.The clearance of 131I-anti-HBsAgFab in blood was faster than that of 131I-S,.(4)The tumor growth inhibition rate in 131I-anti- HBsAgFab-IT mice was higher than that in the LP-treated mice,but lower slightly than that in 131I-S,-IT mice.(5)The hematologic toxicity was significantly lower in 131I-anti-HBsAgFab and IT groups than that in 131I-S,02 and LP groups. Cone I us i on Our results suggest that the 131I-human anti-HBsAgFab has a considerable targeting activity, and provide an evidence for that it can be used as a novel humanized vector for targeting therapy of hepatoma. Intratumoral administration of 131I-human anti-RB sAgFab make that high levels of radiation can be retaided in tumor with significantly lower doses delivered to normal tissue,and provide a more effective regional therapy.