Kaneta Y, Tsukazaki K, Kubushiro K, Aoki R, Sakayori M, Ueda M, Nozawa S
Department of Obstetrics & Gynecology, Keio University School of Medicine, Tokyo.
Jpn J Cancer Res. 1998 May;89(5):583-8. doi: 10.1111/j.1349-7006.1998.tb03301.x.
Missile therapy, which destroys cancer cells specifically, has been advocated as an effective modality for the treatment of carcinoma. We have developed an immunoconjugate consisting of the monoclonal antibody MSN-1 (IgM), which reacts strongly with endometrial adenocarcinomas, combined with a plant hemitoxin named gelonin via a disulfide bond using N-succinimidyl-3-(2-pyridyldithio) propionate and 2-iminothiolane, and examined its selective cytotoxicity in athymic mice. The reductions in resected weights of target tumor cells, at the local site of MSN-1-gelonin immunoconjugate treatment, were 96% with local administration and 75% with caudal vein administration, as compared with the untreated group. There was no weight loss in treated mice. Our results suggest that this MSN-1-gelonin immunoconjugate has potential clinical applications in the treatment of endometrial adenocarcinomas.
导弹疗法能够特异性地破坏癌细胞,已被倡导作为一种治疗癌症的有效方式。我们研发了一种免疫偶联物,它由单克隆抗体MSN-1(IgM)与一种名为相思豆毒蛋白的植物半毒素通过二硫键结合而成,其中单克隆抗体MSN-1能与子宫内膜腺癌强烈反应。我们使用N-琥珀酰亚胺基-3-(2-吡啶二硫基)丙酸酯和2-亚氨基硫醇,通过二硫键将其与相思豆毒蛋白结合,并检测了其在无胸腺小鼠体内的选择性细胞毒性。与未治疗组相比,在MSN-1-相思豆毒蛋白免疫偶联物治疗的局部部位,靶肿瘤细胞切除重量的减少率,局部给药时为96%,尾静脉给药时为75%。治疗的小鼠没有体重减轻。我们的结果表明,这种MSN-1-相思豆毒蛋白免疫偶联物在子宫内膜腺癌的治疗中具有潜在的临床应用价值。