Chen L J, Zhang S Y, Zhang J L, Zhang Z, Li S, Chen M, Zhang X Y, Chen X T
Shanghai Institute of Materia Medica, Chinese Academy of Sciences.
Zhongguo Yao Li Xue Bao. 1993 Nov;14(6):572-6.
An anti-gastric cancer monoclonal antibody MGb2-mitomycin C conjugate via dextran T-70 as intermediate (MGb2-PAD-MMC) was produced, and 28-30 g molecules of MMC were introduced into 1 g molecule of MGb2. Ninety-six hours after ip of 125I-MGb2-PAD-MMC (1.48 MBq/22 micrograms MGb2 per mouse) to nude mice bearing human gastric cancer SGC-7901, the tumor tissue:blood (T/NT) radioactivity ratio was 2.6, very much higher than that of the control 125I-normal IgG-PAD-MMC group (T/NT = 0.20). Single photo computed tomography imaging confirmed the results of biodistribution study. MGb2-PAD-MMC exhibited selective killing action on the SGC-7901 cells in vitro, which was considered to be mediated by monoclonal antibody MGb2. Nude mice inoculated with SGC-7901 xenograft in bilateral subrenal capsule were treated by MMC (ip), human recombinant interferon-alpha (Hu-IFN-alpha im), MGb2-PAD-MMC (ip) and MGb2-PAD-MMC+Hu-IFN-alpha daily for 5 d beginning 4 h after inoculation. The efficacy of the reagents estimated by the reduction of tumor size and calculated by T/C (%), was 28.3%, 16.4%, 47.8%, and 83.1%, respectively. These results demonstrated that the antitumor effect of MGb2-PAD-MMC was superior to free MMC, and that the Hu-IFN-alpha might further enhance the action of MGb2-PAD-MMC.
制备了一种以葡聚糖T-70为中间体的抗胃癌单克隆抗体MGb2-丝裂霉素C偶联物(MGb2-PAD-MMC),每1 g分子的MGb2中引入了28 - 30 g分子的丝裂霉素C。给荷人胃癌SGC-7901裸鼠腹腔注射125I-MGb2-PAD-MMC(每只小鼠1.48 MBq/22 μg MGb2)96小时后,肿瘤组织与血液(T/NT)放射性比值为2.6,远高于对照125I-正常IgG-PAD-MMC组(T/NT = 0.20)。单光子计算机断层扫描成像证实了生物分布研究的结果。MGb2-PAD-MMC在体外对SGC-7901细胞表现出选择性杀伤作用,这被认为是由单克隆抗体MGb2介导的。对双侧肾包膜下接种SGC-7901异种移植物的裸鼠,于接种后4小时开始,每天分别腹腔注射丝裂霉素C(MMC)、皮下注射人重组干扰素-α(Hu-IFN-α)、腹腔注射MGb2-PAD-MMC以及腹腔注射MGb2-PAD-MMC + Hu-IFN-α,连续5天。通过肿瘤体积缩小来评估试剂的疗效,并以T/C(%)计算,结果分别为28.3%、16.4%、47.8%和83.1%。这些结果表明,MGb2-PAD-MMC的抗肿瘤作用优于游离丝裂霉素C,并且Hu-IFN-α可能进一步增强MGb2-PAD-MMC的作用。