免疫药物结合物对裸小鼠肾包膜下接种人胃癌移植瘤生长的影响

Effects of immuno-drug conjugates on growth of human gastric cancer xenograft in subrenal capsule of nude mice

A conjugate of an anti-gastric cancer monoclonal antibody and mitomycin C linked by polyaldehyde dextran T-40 (MGb2-PAD-MMC) was prepared. Nude mice inoculated with human gastric cancer (SGC-7901) xenograft in bilateral subrenal capsule were treated ip with the conjugate at a daily dose containing MGb2 22.4 mg/kg and MMC 1 mg/kg for 6 d since 4 h after inoculation. The efficacy of the conjugate was estimated by the reduction of tumor size which calculated by T/C (%) was 32.2%. If MGb2 in the conjugate was replaced by a normal nude mice IgG (NIgG-PAD-MMC) or the nude mice were treated ip with the dose of MMC alone, the tumor T/C (%) were 58 and 87%, respectively. It was statistically significant between MGb2-PAD-MMC and NIgG-PAD-MMC or MMC treatment. When the above mentioned nude mice with SGC-7901 were treated ip with thrice dose of the conjugate (MGb2 67.2 mg/kg and MMC 3 mg/kg) for 6 d, the tumor growth was inhibited completely. Nevertheless, the same dose of MMC was given to the nude mice resulted in toxic appearance included anorexia, weight loss or even death. Furthermore, when the nude mice were treated ip with MGb2-PAD-MMC 24 h after inoculation, no apparent therapeutic effect was seen. In some experiments, nude mice inoculated with another human transplanted gastric tumor (GA II) xenograft treated ip with a conjugate of MGb2 and MMC or daunorubcin (Dau) 1 day after inoculation.(ABSTRACT TRUNCATED AT 250 WORDS)