發(fā)布時間：2018-03-29 02:16

  本文選題：單克隆抗體　切入點：電荷異質性　出處：《藥物分析雜志》2017年08期

【摘要】：目的:對4種常用的單抗電荷異質性分析方法進行比對研究。方法:以重組抗TNFα全人源單克隆抗體為例,分別利用離子交換色譜(IEC)、毛細管區(qū)帶電泳(CZE)、毛細管等電聚焦電泳(CIEF)和成像毛細管等電聚焦電泳(iCIEF)4種方法對該抗體的電荷異質性進行分析;利用CIEF和iCIEF 2種方法對抗體主峰等電點(pI)進行分析。結果:4種方法能夠對重組抗TNFα全人源單克隆抗體的電荷異構體進行有效的分離和定量,其中IEC和CZE 2種方法檢測的電荷異構體峰面積百分比(酸性峰、主峰和堿性峰)較為一致,4種方法檢測的堿性峰比例較一致,CIEF和iCIEF檢測的主峰與酸性峰比例較其他方法偏高。CIEF和iCIEF檢測抗體主峰等電點具有一定差異,其中,聚焦時間長短和pI Marker的選擇是影響單抗pI值檢測的主要因素。結論:通過抗體電荷異質性分析方法的比較研究可見,在單抗電荷異構體比例和主峰pI測定上4種方法具有一定的差異。對單抗的質控應結合產品特性和表征研究,合理選擇電荷異質性分析方法。
[Abstract]:Objective: to compare and study four common methods for the analysis of the charge heterogeneity of monoclonal antibodies (McAbs). Methods: the recombinant monoclonal antibody against TNF 偽 was used as an example. The charge heterogeneity of the antibody was analyzed by ion-exchange chromatography (IEC), capillary zone electrophoresis (CZE), capillary isoelectric focusing electrophoresis (CIEF) and imaging capillary isoelectric focusing electrophoresis (iCIEF). The main peak isoelectric point (Pi) of the antibody was analyzed by CIEF and iCIEF. Results the charge-isomers of the recombinant anti-human monoclonal antibody against TNF 偽 could be effectively separated and quantified by the two methods. The charge isomer peak area percentage detected by IEC and CZE methods (acid peak, acid peak, acid peak, acid peak, acid peak, acid peak, acid peak, acid peak). The ratio of main peak and acid peak detected by iCIEF and iCIEF were higher than those of other methods, and the isoelectric point of main peak of antibody detected by iCIEF was higher than that of other methods, among them, the ratio of main peak to acid peak was higher than that of other methods, and the ratio of main peak to acid peak was higher than that of other methods. The length of focus time and the selection of Pi Marker are the main factors influencing the detection of Pi value of monoclonal antibody. Conclusion: through the comparison of antibody charge heterogeneity analysis, we can see that, There are some differences in the ratio of charge isomers of McAb and the determination of main peak Pi. The quality control of McAbs should be combined with the study of product characteristics and characterization, and the analysis method of charge heterogeneity should be reasonably selected.
【作者單位】： 中國食品藥品檢定研究院單克隆抗體產品室衛(wèi)生部生物技術產品檢定及標準化重點實驗室;
【基金】：國家“重大新藥創(chuàng)制”科技重大專項資助項目(2014ZX09304311-001,2012ZX09304010)
【分類號】：R392-33

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