Two doses of humanized anti-CD25 antibody in renal transplantation A preliminary comparative study
Two doses of humanized anti-CD25 antibody in renal transplantation A preliminary comparative study
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DOI：
10.4161/mabs.1.1.7399
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发表时间：
2009-01-01
期刊：
影响因子：
5.3
通讯作者：
Guo, Yajun
中科院分区：
文献类型：
--
作者：
Li, Jing;Li, Xinyan;Guo, Yajun
HuCD25mAb是一种人源化抗CD25抗体，其氨基酸序列与daclizumab（Zenapax，Roche）相同。 HuCD25mAb 在中国仓鼠卵巢 (CHO) 细胞中表达，而达珠单抗在 NSO 骨髓瘤细胞系中表达。进行了一项比较研究，以评估 huCD25mAb 和 daclizumab 在结合三重免疫抑制剂治疗方案（MMF、Cs.A 和类固醇）的两剂量方案中的药代动力学和药效学。 15 名患者入组并随机接受手术第 0 天和术后第 14 天静脉输注 huCD25mAb (n = 10) 或 daclizumab (n = 5)，剂量为 1 mg.kg(-1)。通过经过验证的竞争性 ELISA 测量 huCD25mAb 和 daclizumab 的血清浓度。通过流式细胞术定期监测CD3(+)、CD25(+)、CD4(+)和CD8(+)淋巴细胞亚群。发现 huCD25mAb 和 daclizumab 的浓度-时间曲线非常适合单室模型。第0天首次输注后30分钟观察到CD3(-)CD25(+)和CD3(+)CD25(+)淋巴细胞比例(%)显着下降(3.40+/-1.83至0.03+/-0.07、3.35+/-2.02至0.37+/-0.49)，并且这些水平在至少70天内保持较低水平（0.03+/-0.05、0.31+/-0.47）。 huCD25mAb 的所有药代动力学参数似乎与 daclizumab 相似。两剂量huCD25mAb方案在治疗患者中快速达到高治疗浓度方面与达克珠单抗一样有效，并且CD3(-)CD25(+)和CD3(+)CD25(+)淋巴细胞显着减少。这表明两剂量方案在维持宿主免疫抑制方面是可行的，并且可能为降低急性移植物排斥的发生率提供有效且经济的策略。
HuCD25mAb is a humanized anti-CD25 antibody which has the same amino acid sequence as daclizumab (Zenapax, Roche). HuCD25mAb is expressed in Chinese hamster ovary (CHO) cells while daclizumab is expressed in the NSO myeloma cell line. A comparative study was performed to evaluate the pharmacokinetics and pharmacodynamics between huCD25mAb and daclizumab in a two-dose regimen incorporating triple immunosuppressant treatment regimens (MMF, Cs.A and steroids). Fifteen patients were enrolled and randomized to receive intravenous infusion of either huCD25mAb (n = 10) or daclizumab (n = 5) at a dosage of 1 mg.kg(-1) on operation day 0 and post-operation day 14. Serum concentrations of huCD25mAb and dadizumab were measured by a validated competitive ELISA. Subgroups of CD3(+), CD25(+), CD4(+) and CD8(+) lymphocytes were monitored periodically by flow cytometry. The concentration-time curves of huCD25mAb and daclizumab were found to fit well to a one-compartment model. A significant decline of proportion (%) of CD3(-)CD25(+) and CD3(+)CD25(+) lymphocytes was observed 30 min after first infusion on day 0 (3.40 +/- 1.83 to 0.03 +/- 0.07, 3.35 +/- 2.02 to 0.37 +/- 0.49), and these levels remained low for at least 70 days (0.03 +/- 0.05, 0.31 +/- 0.47). All pharmacokinetic parameters of huCD25mAb seemed similar to those of daclizumab. The two-dose huCD25mAb regimen was as effective as daclizumab in rapidly achieving high therapeutic concentration in the treated patients, and a significant decrease of CD3(-)CD25(+) and CD3(+)CD25(+) lymphocytes was demonstrated. This suggests that two-dose regimen is feasible in maintaining host immunosuppression and may provide an effective and economical strategy for reducing incidence of acute graft rejection.