抗乙型肝炎表面抗原Fab片段联合抗细胞核单抗为载体的肝癌放射免疫治疗实验研究

目的 探讨核素标记人源化抗(乙型肝炎)乙肝表面抗原Fab片段(抗HBsAg Fab)联合核素标记抗细胞核单克隆抗体(chTNT)瘤内注射治疗荷人肝癌移植瘤裸鼠的可行性和优越性,为临床应用核素标记多种不同性质的单克隆抗体进行放射免疫治疗肝癌提供实验依据.方法 荷瘤裸鼠分为五组,分别瘤内注射131I-抗HBsAg Fab、131I-chTNT、131I-抗HBsAg Fab联合131I-chTNT、131I-无关抗体(131HgG)及PBS.治疗后行SPECT显像观察标记抗体在肿瘤内的浓聚,并澍量肿瘤大小变化,计算肿瘤抑制率.结果 研究发现2种标记抗体联合应用组的肿瘤抑制率为73.09%,呀显高于131I-抗HBsAgFab组的47.8%和131I-chTNT组的54.26%.联合应用组标记抗体在肿瘤组织/非肿瘤组织内的放射活度比值(T/NT值)大于单独应用组.结论 131I-抗HBsAg Fab联合131I-chTNT瘤内注射放射免疫治疗可增加标记抗体在肿瘤组织内的浓聚.并能提高放射免疫治疗效果.

Radioimmunotherapy with 131I-labeled humanized anti-HBsAg Fab and anti-nucleus antigen monoclonal antibody chTNT in nude mice bearing human hepatocellular carcinoma

OBJECTIVE: To evaluate the feasibility and efficacy of radioimmunotherapy with 131 I-labeled humanized anti-HBsAg Fab (131 I-anti-HBsAg Fab) combined with 131 I-labeled anti-nucleus antigen monoclonal antibody chTNT (131 I-chTNT) in nude mice bearing human hepatocellular carcinoma. METHODS: Nude mice bearing subcutaneous human hepatocellular carcinoma xenografts were treated by intratumoral injection of 131 I-anti-HBsAg Fab and/or 131 I-chTNT, and the changes in the tumor size and alterations in the radioactivity concentration in the tumor and non-tumor tissues were observed. RESULTS: The tumor inhibition rate in mice treated with 131 I-anti-HBsAg Fab combined with 131 I-chTNT (73.09%) was significantly higher than that in mice treated with 131 I-anti-HBsAg Fab (47.8%) or 131 I-chTNT (54.26%) alone. Combined treatment also resulted in significantly higher tumor-to-normal radioactivity concentration ratios than the treatment with the single agents. CONCLUSION: Intratumoral injection with 131 I-labeled monoclonal antibodies can increase the radioactivity concentration in the tumor and enhance the efficacy of the radioimmunotherapy in nude mice bearing human hepatocellular carcinoma.