肝癌“双弹头”组合单抗导向治疗的实验研究

The Experimental Studies of "Double Bomb"-Mixed Monoclonal Antibody for Hepatocellular Carcinoma

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。

Two monoclonal antibodies of high specificity and high affinity against hepatocellular carcinorna HAb18,HAb25 as carriers,and131Ⅰand adriamycin (ADM) as warheads,'in the form of double bomb'-mixed monodonal antibodies immunoconjugates(131Ⅰ-HAb18-ADM)/(131Ⅰ-HAb25-ADM) were prepared by technic of indirectly conjugating with dextron T-40 and chloramin-T.The rate of its immunocombining power to target cells was 42. 5%,labeling rate 49,8%,specific radioactivity 6. 88×1010Bq/ug.In vitro(131Ⅰ-HAb18-ADM)/(131Ⅰ-HAb25-ADM)showed stronger selective cytotoxicity against target tumor cells than any of the conjugates HAb18-HAb25-ADM),131-HAb,HAb25-ADM,or13Ⅰ-HAb alone(P<0.05).The(131Ⅰ-HAb18-ADM)/(131Ⅰ-HAb18-ADM) targeting therapy in nude mice bearing human hepatocellular carcinoma showed that,tumor/liver was 3. 735±0. 120, inhibitory effect was stronger than' single bomb' or' single antibody'(P<0.05).These results indicate that,this'double bomb' played effect of both chemotherapy and radiotherapy and that'mixed antibody' rreduced the effect of tumor on targetting therapy.