肾移植术后单剂应用人源化抗CD3单克隆抗体的临床观察

目的 研究肾移植受者体内应用人源化抗CD3单克隆抗体(OKT3)注射液单次剂量递增给药后的短期和长期安全性.方法 2008年6-12月,共29例肾功能稳定的尸体肾移植受者入选该研究.每位受试者按入组顺序随机分至2.5 mg(n=9)、5.0 mg(n=10)、10.0 mg(n=10)3个剂量组,并于移植术后7～14 d内接受相应剂量的OKT3单次给药.同时选取同期未参加试验的30例肾移植受者作为对照组.所有患者至少随访2年,随访期间监测肝功能、肾功能、血常规等指标,并观察有无其他不良事件.结果 各剂量组受试者在给药后48 h内,出现低热(7/29)、畏寒(4/29)、肝功能损害(2/29)、上呼吸道感染(1/29)和头痛(1/29),未出现明显的首剂效应,其余的不良反应轻微,发生率与剂量无关.随访期间内,试验组和对照组2-年人/肾长期存活率分别为100%/100%和100%/97%;移植肾活检证实的急性排斥发生率分别为6.9%(2/29)和10.0%(3/30),肺部感染发生率分别为10.3%(3/29)和13.3%(4/30).术后1周及3、6、12、24个月监测血肌酐值显示,两组差异均无统计学意义(均P＞0.05).结论 人源化OKT3不同剂量单次给药在肾移植受者体内安全性良好,其有望成为一种抗排斥能力强、毒副作用较小的免疫抑制剂.

Abstract：

Objective To evaluate short-term and long-term safety of using single-dose escalation of recombinant humanized anti-CD3 monoclonal antibody (OKT3) in kidney transplantation recipients.Methods A total of 29 recipients of cadaveric kidney transplant from June 2008 to December 2008 were sequently assigned to receive single-dose intravenous injection of OKT3 with different doses of 2. 5 mg( n =9) , 5.0 mg (n = 10) and 10. 0 mg (n = 10) at Days 7 - 14 post-operation. Meanwhile, a control group was established by selecting kidney transplant recipients, who did not participate in the trial in the same period.All patients were followed up for at least 2 years. During this period, liver function, kidney function,hemoglobin and other biochemical indicators were monitored and adverse events recorded over time. Results No obvious first dose effect was observed,except low heat (7/29), chills (4/29) , mild liver damage (2/29) , upper respiratory tract infection and headache (1/29) across all doses. Other adverse reactions were mild, unrelated with doses. The 2-year patients/ grafts survival rates of treatment goup and control group were 100% / 100%, and 100% / 97%, respectively. The incidence of acute rejection confirmed by renal biopsy was 6. 9% (2/29) and 10. 0% (3/30) in treatment group and control group, respectively. The incidence of lung infection was 10. 3% ( 3/29 ) and 13.3% ( 4/30 ), respectively. The values of serum creatinine at 1 week and 3, 6, 12, 24 months showed no statistically significance in two groups ( all P ＞0. 05). Conclusion It is safe to use single-shot OKT3 intravenously in kidney transplant recipients. The recombinant humanized OKT3 may be an effective immunosuppressive agent with milder toxicity for solid organ transplantation.

Clinical study of single-dose of recombinant humanized anti-CD3 monoclonal antibody injection in kidney transplant recipients

Objective To evaluate short-term and long-term safety of using single-dose escalation of recombinant humanized anti-CD3 monoclonal antibody (OKT3) in kidney transplantation recipients.Methods A total of 29 recipients of cadaveric kidney transplant from June 2008 to December 2008 were sequently assigned to receive single-dose intravenous injection of OKT3 with different doses of 2. 5 mg( n =9) , 5.0 mg (n = 10) and 10. 0 mg (n = 10) at Days 7 - 14 post-operation. Meanwhile, a control group was established by selecting kidney transplant recipients, who did not participate in the trial in the same period.All patients were followed up for at least 2 years. During this period, liver function, kidney function,hemoglobin and other biochemical indicators were monitored and adverse events recorded over time. Results No obvious first dose effect was observed,except low heat (7/29), chills (4/29) , mild liver damage (2/29) , upper respiratory tract infection and headache (1/29) across all doses. Other adverse reactions were mild, unrelated with doses. The 2-year patients/ grafts survival rates of treatment goup and control group were 100% / 100%, and 100% / 97%, respectively. The incidence of acute rejection confirmed by renal biopsy was 6. 9% (2/29) and 10. 0% (3/30) in treatment group and control group, respectively. The incidence of lung infection was 10. 3% ( 3/29 ) and 13.3% ( 4/30 ), respectively. The values of serum creatinine at 1 week and 3, 6, 12, 24 months showed no statistically significance in two groups ( all P ＞0. 05). Conclusion It is safe to use single-shot OKT3 intravenously in kidney transplant recipients. The recombinant humanized OKT3 may be an effective immunosuppressive agent with milder toxicity for solid organ transplantation.