Bioprocess development of antibody-drug conjugate production for cancer treatment.
Bioprocess development of antibody-drug conjugate production for cancer treatment.
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DOI：
10.1371/journal.pone.0206246
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发表时间：
2018
期刊：
影响因子：
3.7
通讯作者：
Liu X
中科院分区：
文献类型：
--
作者：
Ou J;Si Y;Goh K;Yasui N;Guo Y;Song J;Wang L;Jaskula-Sztul R;Fan J;Zhou L;Liu R;Liu X
抗体-药物偶联物（Antibody-drug conjugate，ADC）是一种结合单克隆抗体（monoclonal antibody，mAb）的特异性靶向性和化疗药物的细胞毒性的联合收割机。ADC的治疗效果受其生物生产过程的显著影响。本研究旨在开发一种使用抗HER 2 mAb药物作为模型治疗剂的有效ADC生产工艺。首先，通过来自补料分批细胞培养的中国仓鼠卵巢细胞产生高滴度（> 2g/L）的mAb。活细胞共聚焦显微镜成像和流式细胞术分析均证明所产生的mAb和ADC与HER 2+细胞系BT474具有强且特异性的结合。其次，研究了mAb和药物的各种偶联条件，包括接头的选择、药物和mAb的比例以及偶联方法，以提高产量和产品质量。最后，通过SDS-PAGE和抗乳腺癌毒性实验分别对ADC的结构和生物学质量进行评价。使用优化的生产工艺生产了具有完整分子结构和高细胞毒性（IC 50为1.95 nM）的ADC。稳健的生物生产过程可以指导基于ADC的生物药物的开发。
Antibody-drug conjugate (ADC) is a class of targeted cancer therapies that combine the advantages of monoclonal antibody (mAb)’s specific targeting and chemotherapy’s potent cytotoxicity. The therapeutic effect of ADC is significantly affected by its bioproduction process. This study aims to develop an effective ADC production process using anti-HER2 mAb-drug as a model therapeutic. First, a high titer (>2 g/L) of mAb was produced by Chinese hamster ovary cells from fed-batch cell culture. Both live-cell confocal microscopy imaging and flow cytometry analysis demonstrated that the produced mAb and ADC had strong and specific binding to HER2+ cell line BT474. Second, various conjugation conditions of mAb and drug, including linker selection, ratio of drug and mAb, and conjugation approaches, were investigated to improve the production yield and product quality. Finally, the ADC structure and biological quality were evaluated by SDS-PAGE and anti-breast cancer toxicity study, respectively. The ADC with integral molecular structure and high cytotoxicity (IC50 of 1.95 nM) was produced using the optimized production process. The robust bioproduction process could guide the development of ADC-based biopharmaceuticals.
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影响因子：
4.6
作者：
Nejadmoghaddam MR;Zarnani AH;Ghahremanzadeh R;Ghods R;Mahmoudian J;Yousefi M;Nazari M;Ghahremani MH;Abolhasani M;Anissian A;Mahmoudi M;Dinarvand R
通讯作者：
Dinarvand R
影响因子：
2.7
作者：
Bouchard, Herve;Viskov, Christian;Garcia-Echeverria, Carlos
通讯作者：
Garcia-Echeverria, Carlos
影响因子：
2.9
作者：
Hofer T;Skeffington LR;Chapman CM;Rader C
通讯作者：
Rader C
DOI：
10.1016/j.jtho.2016.01.012
发表时间：
2016-04
期刊：
Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer
影响因子：
--
作者：
Bunn PA Jr;Minna JD;Augustyn A;Gazdar AF;Ouadah Y;Krasnow MA;Berns A;Brambilla E;Rekhtman N;Massion PP;Niederst M;Peifer M;Yokota J;Govindan R;Poirier JT;Byers LA;Wynes MW;McFadden DG;MacPherson D;Hann CL;Farago AF;Dive C;Teicher BA;Peacock CD;Johnson JE;Cobb MH;Wendel HG;Spigel D;Sage J;Yang P;Pietanza MC;Krug LM;Heymach J;Ujhazy P;Zhou C;Goto K;Dowlati A;Christensen CL;Park K;Einhorn LH;Edelman MJ;Giaccone G;Gerber DE;Salgia R;Owonikoko T;Malik S;Karachaliou N;Gandara DR;Slotman BJ;Blackhall F;Goss G;Thomas R;Rudin CM;Hirsch FR
通讯作者：
Hirsch FR
影响因子：
2.2
作者：
Junutula, Jagath R.;Bhakta, Sunil;Lowman, Henry B.
通讯作者：
Lowman, Henry B.