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以肝癌单抗HAb18、HAb25为载体,以131Ⅰ、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131Ⅰ-HAb18-ADM/131Ⅰ-HAb25-ADM,其标记率49.8%,比放射性6.88×104Bq/ug,免疫结合率42.5%。细胞毒实验结果显示“双单头”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)。荷瘤鼠导向治疗实验,168小时SPECT扫描定位清晰,瘤/肝比值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;组合单抗较好消除了肿瘤异质性对导向治疗的影响。
Using hepatoma monoclonal antibodies HAb18 and HAb25 as vectors and 131I and adriamycin (ADM) as warheads, indirect cross-linking and chloramine T method were used to prepare the “targeted” combination antibody monoclonal antibody immunohistochemical 131I-HAb18- ADM/131I-HAb25-ADM has a labeling rate of 49.8%, a specific radioactivity of 6.88×104 Bq/ug, and an immunocombination rate of 42.5%. The results of cytotoxicity test showed that the killing power of the “double-headed” combination monoclonal antibody conjugate was significantly stronger than that of the single-headed single antibody conjugate (P < 0.05). Tumor-bearing mice were targeted to the treatment experiment. The 168-hour SPECT scan was well-defined. The tumor/liver ratio was 3.735±0.120, and the treatment effect was significantly stronger than other groups (P<0.05). The above results indicate that the “dual warheads” focus on the advantages of chemotherapy and radiotherapy, and that the two are synergistic and improve the killing effect. The combination of monoclonal antibodies can better eliminate the influence of tumor heterogeneity on targeted therapy.