本文選題：重組人源單克隆抗體　切入點：rhuIgG-　出處：《中國生物制品學(xué)雜志》2016年07期 　論文類型：期刊論文

【摘要】：目的建立重組人源單克隆抗體rhu Ig G-04臨床研究中免疫原性檢測方法。方法建立由篩選法(橋連ELISA法)和確證法(免疫清除法)組成的多重檢驗方法檢測重組人源單克隆抗體rhu Ig G-04臨床研究中的免疫原性,并對方法進(jìn)行優(yōu)化,利用含有人Ig G(Fc)的融合蛋白去除類風(fēng)濕因子(rheumatoid factor,RF)的干擾;通過統(tǒng)計大量空白血清信號值及信號抑制率,確定篩選法和確證法的臨界值。在篩選法中確定了歸一化因子對不同批次的臨界值進(jìn)行歸一化處理。分析檢測法對血清中rhu Ig G-04的耐受性。結(jié)果篩選法中,樣品最佳稀釋倍數(shù)為1/10,最佳稀釋液為PBS,二抗rhu Ig G-04-HRP的最適稀釋度為1/10 000;在二抗中加入濃度為1 mg/ml Fc片段的融合蛋白能有效去除RF的干擾;歸一化因子為0.006,批檢測臨界值為陰性對照品A值+歸一化因子;血清中藥物濃度達(dá)到1 200 ng/ml時,對篩選法結(jié)果無影響。確證法中,向樣品中加入rhu Ig G-04的適宜濃度為100μg/ml,確證法臨界值為49%。結(jié)論建立的免疫原性檢測方法具有較高的檢測靈敏度,抗藥物干擾能力強(qiáng),達(dá)到了抗體藥物免疫原性檢測方法的基本要求,為人源單抗rhu Ig G-04免疫原性的檢測提供了適宜的手段。
[Abstract]:Objective to establish a method for the detection of immunogenicity of recombinant human monoclonal antibody (rhu Ig G-04) in clinical study. Immunogenicity of monoclonal antibody rhu Ig G-04 in clinical studies, The method was optimized to remove the interference of rheumatoid factor (RF) by using fusion protein containing human Ig Gfc, and a large number of blank serum signal values and signal inhibition rates were calculated. The critical value of screening method and confirmatory method was determined. In the screening method, the normalized factor was determined to normalize the critical value of different batches. The tolerance of the detection method to rhu Ig G-04 in serum was analyzed. The optimal dilution ratio was 1 / 10, the optimal dilution was PBSs, the optimal dilution of second antibody Ig G-04-HRP was 1/10 000, the fusion protein with 1 mg/ml FC fragment in the second antibody could effectively remove the interference of RF. The normalization factor is 0.006, the critical value of batch detection is negative reference substance A normalized factor, and the concentration of drug in serum reaches 1 200 ng/ml, which has no effect on the results of screening method. The suitable concentration of rhu Ig G-04 was 100 渭 g / ml, and the critical value of confirmation method was 49 渭 g / ml. Conclusion the established immunogenicity detection method has high detection sensitivity and strong ability of anti-drug interference. The method of immunogenicity detection of human monoclonal antibody rhu Ig G-04 has been met with the basic requirements of antibody immunogenicity detection method, which provides a suitable method for the detection of immunogenicity of human monoclonal antibody rhu Ig G-04.
【作者單位】： 華北制藥集團(tuán)新藥研究開發(fā)有限責(zé)任公司;
【基金】：“重大新藥創(chuàng)制”國家科技重大專項創(chuàng)新型人源單抗藥物研制平臺及重大品種開發(fā)(2014ZX09201041)
【分類號】：R392-33

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