Ohkawa K, Tsukada Y, Umemoto N, Hara T
Gan To Kagaku Ryoho. 1986 Mar;13(3 Pt 1):563-9.
The anti-cancer drug, mitomycin C (MMC), was conjugated to an affinity-purified horse antibody to human alpha-fetoprotein (aAFP) via purified human serum albumin (HSA) as an intermediate carrier. The conjugate (aAFP immunoglobulin (IgG): HSA: MMC, molar ratio 1: 1.10:29.8) was 21 or 38 times as cytotoxic as free MMC or PBS at the MMC concentration of 100 ng/ml, respectively, against alpha-fetoprotein-producing human yolk sac tumor in vitro. The in vivo effects of the conjugate and various controls were also tested against human yolk sac tumor growing in nude mice. The conjugate over a total of 6 injections retarded the initial tumor growth at the concentration of MMC, containing equivalent amounts of 2 micrograms/mouse (0.1 mg/kg)/injection in the conjugate, whereas free MMC and normal horse IgG-HSA-MMC showed only slight inhibitory effects alone at non-toxic levels. These results suggest that the specific antibody-conjugate was considerably more effective than free MMC against the tumor maintained in nude mice as well as in vitro cultures.
抗癌药物丝裂霉素C(MMC)通过纯化的人血清白蛋白(HSA)作为中间载体与亲和纯化的抗人甲胎蛋白(aAFP)马抗体偶联。该偶联物(aAFP免疫球蛋白(IgG):HSA:MMC,摩尔比为1:1.10:29.8)在MMC浓度为100 ng/ml时,对产生甲胎蛋白的人卵黄囊瘤的细胞毒性分别是游离MMC或PBS的21倍或38倍。还针对裸鼠体内生长的人卵黄囊瘤测试了该偶联物和各种对照的体内效果。在总共6次注射中,该偶联物在MMC浓度为每只小鼠含等量2微克(0.1毫克/千克)/注射时,延缓了肿瘤的初始生长,而游离MMC和正常马IgG-HSA-MMC在无毒水平时单独仅显示出轻微的抑制作用。这些结果表明,特异性抗体偶联物在对抗裸鼠体内维持的肿瘤以及体外培养物方面比游离MMC有效得多。