Selective in vitro and in vivo growth inhibition against human yolk sac tumor cell lines by purified antibody against human α-fetoprotein conjugated with mitomycin C via human serum albumin
Selective in vitro and in vivo growth inhibition against human yolk sac tumor cell lines by purified antibody against human α-fetoprotein conjugated with mitomycin C via human serum albumin
复制标题
通过人血清白蛋白与丝裂霉素 C 结合的纯化抗人甲胎蛋白抗体对人卵黄囊肿瘤细胞系的体外和体内选择性生长抑制
DOI：
10.1007/bf00199811
复制
发表时间：
2004
期刊：
影响因子：
--
通讯作者：
T. Hara
中科院分区：
文献类型：
--
作者：
K. Ohkawa;Y. Tsukada;N. Hibi;N. Umemoto;T. Hara
以人血清白蛋白（HSA）为中间药物载体，将抗癌药物丝裂霉素C（MMC）与亲和纯化的马抗人甲胎蛋白（aAFP）抗体偶联。通过竞争性结合放射免疫测定法测定，缀合物（aAFP：HSA：MMC摩尔比，1：1：30）保留完全抗体结合活性。在细胞毒性试验中，将产生AFP的人卵黄囊肿瘤TG-1细胞与试验材料预孵育2 h，然后在新鲜培养基中再培养48 h，在等效MMC浓度为100 ng/ml时，缀合物的细胞毒性比游离MMC高20倍。针对在无胸腺裸鼠中生长的人卵黄囊肿瘤JOG-9测试缀合物的体内抗肿瘤作用。当荷瘤小鼠接受连续2天共6次注射，然后从SC肿瘤接种后第8天开始每隔一天注射一次[每次注射2（等效MMC）μg/头]时，结合物比游离MMC和正常马免疫球蛋白结合物更有效地延缓肿瘤生长。
The anticancer drug mitomycin C (MMC) was conjugated with an affinity-purified horse antibody to human α-fetoprotein (aAFP) with human serum albumin (HSA) as the intermediate drug carrier. The conjugate (aAFP:HSA:MMC molar ratio, 1:1:30) retained full antibody binding activity as determined by a competitive binding radioimmunoassay. In a cytotoxicity test in which the AFP-producing human yolk sac tumor TG-1 cells were preincubated with test materials for 2 h followed by an additional 48-h culture in fresh medium, the conjugate was 20-fold more cytotoxic than free MMC at an equivalent MMC concentration of 100 ng/ml. The in vivo antitumor effect of the conjugate was tested against the human yolk sac tumor JOG-9 growing in athymic nude mice. When the tumor-bearing mice were treated with a total of 6 injections given on 2 consecutive days and then every other day starting 8 days after SC tumor inoculation [2 (equivalent MMC) μg/head per injection], the conjugate retarded tumor growth more effectively than free MMC and normal horse immunoglobulin conjugate.