Tsukada Y
Gan To Kagaku Ryoho. 1985 Mar;12(3 Pt 2):741-50.
In order to increase the selective localization of anti-cancer drugs to the target tumor cells, polyclonal or monoclonal anti alpha-fetoprotein antibody (aAFP) was conjugated with anti-cancer drugs such as daunomycin (DM), adriamycin (AM) and mitomycin C (MMC) by chemical modification. Dextran (Dex) or poly L-glutamic acid (PLGA) was used to bind aAFP with DM (AM) as an intermediate drug carrier. For the conjugation of aAFP with MMC, a direct binding method through the aziridine ring of the activated MMC derivative or an indirect binding method through serum albumin as an intermediate drug carrier was employed. These conjugates caused greater inhibition of both in vitro and in vivo tumor growth of AFP-producing target tumor cells than did a mixture of aAFP and anti-cancer drugs or a simular conjugate of these drugs with normal horse immunoglobulin. AFP has high affinity to unsaturated fatty acids (UFA) such as arachidonic acid (C20:4) and so on. The antitumor effect of UFA-DM conjugate was also assessed using AFP-producing rat ascites hepatoma cells. It was found that UFA-DM conjugated showed highly selective cytocidal effects against the hepatoma cells.
为增加抗癌药物对靶肿瘤细胞的选择性定位，通过化学修饰将多克隆或单克隆抗甲胎蛋白抗体（aAFP）与柔红霉素（DM）、阿霉素（AM）和丝裂霉素C（MMC）等抗癌药物偶联。使用右旋糖酐（Dex）或聚-L-谷氨酸（PLGA）作为中间药物载体，将aAFP与DM（AM）结合。对于aAFP与MMC的偶联，采用通过活化的MMC衍生物的氮丙啶环的直接结合方法或通过血清白蛋白作为中间药物载体的间接结合方法。与aAFP和抗癌药物的混合物或这些药物与正常马免疫球蛋白的类似偶联物相比，这些偶联物对产生AFP的靶肿瘤细胞的体外和体内肿瘤生长均具有更大的抑制作用。AFP与不饱和脂肪酸（UFA）如花生四烯酸（C20:4）等具有高亲和力。还使用产生AFP的大鼠腹水肝癌细胞评估了UFA-DM偶联物的抗肿瘤作用。发现UFA-DM偶联物对肝癌细胞显示出高度选择性的杀细胞作用。
