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Specific chemothrapy for perineural invasion of biliary tract cancer with conjugate of anticancer drug and anti-neural cell adhesion molecule antibody

抗癌药物与抗神经细胞粘附分子抗体偶联物治疗胆道癌神经周围浸润的特异性化疗

基本信息

批准号：
06671240
负责人：
TANAKA Jun-ichi
金额：
$ 1.22万
依托单位：
AKITA UNIVERSITY
依托单位国家：
日本
项目类别：
Grant-in-Aid for General Scientific Research (C)
财政年份：
1994
资助国家：
日本
起止时间：
1994 至 1995
项目状态：
已结题

项目摘要

Conjugate of chemotherapeutic drug (Mitomycin C,MMC) and monoclonal antibody, which was anti-Neural cell adhesion molecule (NCAM) antibody was prepared and evaluated anticancer activity and antibody activity of the conjugate in vitro. MMC and anti-NCAM antibody conjugate was prepared according to Suzuki et al with cyanogen bromide (BrCN) method.The degree of substitution was determined spectrophotometrically by assuming that MMC has absorbance with lambdamax=363nm, E1%1cm=623 and IgG has absorbance with lambda max=280nm, E1%/1cm=13.5. The degree of substitution which was calculated as follows : degree of substitution=mol concentration of drug contained in conjugate/mol concentration of antibody contained in conjugate, was 3.5 (average).A drug activity of conjugate, which was tested by MTT method of the growth inhibition with neuroblastoma cell line (IMR-32) was maintained 66 to 95% compared with same concentration of MMC solution.Antibody activity of conjugate, which was examined by immunohistochemical staining with Avidin-Biotinylated enzyme Complex on NCAM positive bile duct cancer, showed the same level as that of antibody alone.In conclusion, MMC could be linked to anti-NCAM monoclonal antibody by BrCN method. Since this conjugate has both activity of drug and antibody, it can provide an useful tool for specific targeting cancer chemotherapy.

制备了化疗药物丝裂霉素C（MMC）与抗神经细胞粘附分子（NCAM）单克隆抗体的偶联物，并对偶联物的抗肿瘤活性和抗体活性进行了体外评价。采用Suzuki等的溴化氰法制备MMC与抗NCAM抗体偶联物，并通过假设MMC具有λ max = 363 nm，E1%/1cm =623的吸光度，IgG具有λ max= 280 nm，E1%/1cm=13.5的吸光度，用比色法测定取代度。取代度计算如下：取代度=偶联物中所含药物的摩尔浓度/偶联物中所含抗体的摩尔浓度，为3.5（平均值）。用MTT法检测其对神经母细胞瘤细胞株（IMR-32）的生长抑制率为66 ~ 95%用亲和素-生物素化酶复合物免疫组化染色法检测偶联物对NCAM阳性胆管癌的抗体活性，结果显示偶联物的抗体活性与单独抗体的抗体活性相当。通过BrCN方法，MMC可以与抗NCAM单克隆抗体连接。由于该偶联物同时具有药物和抗体的活性，它可以为特异性靶向肿瘤化疗提供有用的工具。