Antitumor effect of anti-epidermal growth factor receptor monoclonal antibodies plus cis-diamminedichloroplatinum on well established A431 cell xenografts.
Antitumor effect of anti-epidermal growth factor receptor monoclonal antibodies plus cis-diamminedichloroplatinum on well established A431 cell xenografts.
复制标题
DOI：
--
复制
发表时间：
1993-10
期刊：
影响因子：
11.2
通讯作者：
Z. Fan;J. Baselga;H. Masui;J. Mendelsohn
中科院分区：
文献类型：
--
作者：
Z. Fan;J. Baselga;H. Masui;J. Mendelsohn
我们已经探索了抗表皮生长因子受体单克隆抗体（MAb）225和528对良好建立的A431表皮样癌异种移植物的治疗效果，在治疗开始时约400 mm 3（直径1 cm）。在以前的报告中，我们证明，单克隆抗体225和528防止肿瘤细胞接种当天开始治疗的裸鼠A431细胞异种移植物的生长。由于抗表皮生长因子受体单克隆抗体治疗已建立的肿瘤无法延缓生长，我们探讨了单克隆抗体加化疗剂顺式二氯二氨铂（顺式DDP）的联合治疗。在A431细胞培养物中观察到单克隆抗体与顺式顺铂的相加和浓度依赖性生长抑制作用。225 MAb强化治疗（1 mg/小鼠，肿瘤接种后第8天腹腔注射，每周两次，持续4周）和最大耐受单次剂量的顺式DDP [150微克/25 g（6 mg/kg）小鼠体重，第8天腹腔注射]对肿瘤生长均无显著影响。然而，与未处理的对照组和用单一方式处理的动物相比，两种处理组合导致显著的异种移植物生长抑制。10天后加入第二剂顺式DDP（150微克/25克），与225单抗联合治疗产生了显著的抗肿瘤作用。在1个月结束时，除一只小鼠外，所有小鼠的肿瘤异种移植物均消失，并且在6个月的观察期间未发生肿瘤复发。抗表皮生长因子受体单克隆抗体528与顺式顺铂联合使用获得了相同的结果。这些研究的结果提供了一种新的方法来治疗建立良好的肿瘤异种移植物，这可能在人类恶性肿瘤的治疗中有应用。
We have explored the therapeutic effects of anti-epidermal growth factor receptor monoclonal antibodies (MAbs) 225 and 528 on well established A431 epidermoid carcinoma xenografts, approximately 400 mm3 (1 cm in diameter) at the start of treatment. In previous reports we demonstrated that MAbs 225 and 528 prevented the growth of A431 cell xenografts in nude mice when treatment was begun on the day of tumor cell inoculation. Since anti-epidermal growth factor receptor MAb therapy of well established tumors was unable to retard growth, we explored combination therapy with MAb plus the chemotherapeutic agent cis-diamminedichloroplatinum (cis-DDP). Additive and concentration-dependent growth-inhibitory effects of MAb with cis-DDP were observed in cultures of A431 cells. Neither intensive treatment with 225 MAb (1 mg/mouse, i.p. on day 8 after tumor inoculation, and twice weekly for 4 weeks) nor a maximally tolerated single dose of cis-DDP [150 micrograms/25 g (6 mg/kg) mouse weight, i.p. on day 8] had significant effects on tumor growth. However, the two treatments in combination resulted in substantial xenograft growth inhibition, compared with both an untreated control group and animals treated with a single modality. When a second dose of cis-DDP (150 micrograms/25 g) was added after 10 days, combination therapy with 225 MAb produced striking antitumor effects. At the end of 1 month tumor xenografts had disappeared in all but one mouse, and no tumor relapses occurred during 6 months of observation. Identical results were obtained with anti-epidermal growth factor receptor MAb 528 in combination with cis-DDP. The results of these studies provide a novel approach to the treatment of well established tumor xenografts, which may have application in the therapy of human malignancies.