肝癌组合单抗导向治疗的实验研究

Experimental studies on targeting-therapy of "double bomb"-Mixed monoclonal antibodies immunoconjugates against hepatocellular carcinoma

以肝癌单抗HAb_(18)、HAb_(25)为载体,以^(131)I、阿霉素(ADM)为弹头,应用间接交联及氯胺T法,制备出肝癌双弹头组合单抗免疫导向结合物^(131)I-HAb_(18)-ADM/^(131)I-HAb_(25)-ADM,其标记率为49.89％,比放射性为6.88×10~4Bq/g,免疫结合率为42.5％。细胞毒实验结果显示双弹头组合单抗结合物杀伤力显著强于单弹头单抗体结合物(P<0.05)。荷肝癌裸鼠导向治疗实验,168小时SPECT扫描定位清晰,瘤/肝比值为3.735±0.120,治疗效果显著强于其它各组(P<0.05)。上述结果表明,双弹头集中了化疗与放疗的优点,二者协同,提高了杀伤效应;组合单抗较好的消除了肿瘤异质性对导向治疗的影响。

Two highly specific monoclonal antibodies with potentul affinity against hepatocellular carcinoma HAb18, HAb25 as carriers, 131I and adriamycin (ADM) as warhead 'double bomb'-mixed monoclonal antibodies immunoconjugates(131I-HAb18-ADM)/(131I-HAb25-ADM) was prepared by indirectly conjugated with dextran T-40 and chloramine-T methods. The immunoconjugating rate to target cells was 42.5%, labelling rate 49.8%, and specific radioactivity 6.88×104Bq/μg. In vitro, (131I-HAb18-ADM)/(131I-HAb25-ADM) showed stronger selective cytotoxicity against target tumor cells than either HAb18-ADM, or 131I-HAb18, or HAb25-ADM, or 131I-HAb25 conjugate alone(P<0.05). The (131I-HAb18-ADM)/(131I-HAb25-ADM) targeting therapy in nude mice bearing human hepatocellular carcinoma showed that, tumor/liver ratio was 3.735±0.120, the inhibitory effect was stronger than 'single bomb' or 'single antibody' (P<0.05). The above results indicate, 'double bomb' has both chemotherapeutic and radiotherapeutic as well as cytotoxic effects which raise the killing effects, and 'mixed antibodies' can eliminate the tumor heterogeneity to some extent.