|
|
|
| Effects of Host Cell Residual Proteins on the Quality and Their Quality Control of Monoclonal Antibody |
LIU Guo-fang,LIU Xiao-zhi,GAO Jian,WANG Zhi-ming( ) |
| State Key Laboratory of Antibody Research & Development,New Drug Research and Development Company Ltd,North China Pharmaceutical Corporation,Shijiazhuang 050015,China |
|
|
|
Abstract The sales of biologic drugs represented by monoclonal antibodies (mAbs) are expanding and showing a rising trend. The use of mAbs provides a new strategy for disease treatment.With the increase in the use of mAbs,higher requirements are placed on the quality of the product.As the level of mAbs expressed by the host cells continues to increase,the content of host cell proteins (HCP) also increases,and the upstream and downstream production processes are constantly faced challenge.The protein contained in HCP is extremely complicated.Although some HCP may be degraded, residual HCP may cause adverse reactions in the clinical use of the drug, thereby affecting the safety and effectiveness of the drug.Enzyme-linked immune sorbent assays (ELISAs) are important methods for HCP detection. ELISAs can quantitatively measure total HCP levels in drugs, but there are limitations.HCP testing of various analytical methods,including LC-MS/MS,is under development,which will provide more evidence for drug process development and validation.The advances in quality control and assays for HCP production in the production of mAbs hosted by the CHO (Chinese hamster ovary) cell line were discussed.
|
|
Received: 29 January 2019
Published: 12 November 2019
|
|
|
|
Corresponding Authors:
Zhi-ming WANG
E-mail: wzm3994@163.com
|
|
|
| [1] |
Hanania N A, Noonan M, Corren J , et al. Lebrikizumab in moderate-to-severe asthma:pooled data from two randomised placebo-controlled studies. Thorax, 2015,70(8):748-756.
|
|
|
| [2] |
Wullner D, Zhou L, Bramhall E , et al. Considerations for optimization and validation of an in vitro PBMC derived T cell assay for immunogenicity prediction of biotherapeutics. Clinical Immunology, 2010,137(1):5-14.
|
|
|
| [3] |
Joubert M K, Deshpande M, Yang J , et al. Use of in vitro assays to assess immunogenicity risk of antibody-based biotherapeutics. PLoS One, 2016,11(8):e0159328.
|
|
|
| [4] |
Bailey-Kellogg C, Gutierrez A H, Moise L , et al. CHOPPI:a web tool for the analysis of immunogenicity risk from host cell proteins in CHO-based protein production. Biotechnology and Bioengineering, 2014,111(11):2170-2182.
doi: 10.1002/bit.25286
|
|
|
| [5] |
Eon-Duval A, Valax P, Solacroup T , et al. Application of the quality by design approach to the drug substance manufacturing process of an Fc fusion protein:towards a global multi-step design space. Journal of Pharmaceutical Sciences, 2012,101(10):3604-3618.
doi: 10.1002/jps.23273
|
|
|
| [6] |
Bracewell D G, Francis R, Smales C M . The future of host cell protein (HCP) identification during process development and manufacturing linked to a risk-based management for their control. Biotechnology and Bioengineering, 2015,112(9):1727-1737.
|
|
|
| [7] |
Zhang Y B, Howitt J, Mccorkle S , et al. Protein aggregation during overexpression limited by peptide extensions with large net negative charge. Protein Expression and Purification, 2004,36(2):207-216.
doi: 10.1016/j.pep.2004.04.020
|
|
|
| [8] |
Kim J Y, Kim Y G, Baik J Y , et al. A proteomic approach for identifying cellular proteins interacting with erythropoietin in recombinant Chinese hamster ovary cells. Biotechnology Progress, 2010,26(1):246-251.
|
|
|
| [9] |
Bee J S, Tie L, Johnson D , et al. Trace levels of the CHO host cell protease cathepsin D caused particle formation in a monoclonal antibody product. Biotechnology Progress, 2015,31(5):1360-1369.
|
|
|
| [10] |
Lauer T M, Agrawal N J, Chennamsetty N , et al. Developability index: a rapid in silico tool for the screening of antibody aggregation propensity. Journal of Pharmaceutical Sciences, 2012,101(1):102-115.
doi: 10.1002/jps.22758
|
|
|
| [11] |
Chiu J, Valente K N, Levy N E , et al. Knockout of a difficult-to-remove CHO host cell protein, lipoprotein lipase, for improved polysorbate stability in monoclonal antibody formulations. Biotechnology and Bioengineering, 2017,114(5):1006-1015.
|
|
|
| [12] |
Valente K N, Lenhoff A M, Lee K H . Expression of difficult-to-remove host cell protein impurities during extended Chinese hamster ovary cell culture and their impact on continuous bioprocessing. Biotechnology and Bioengineering, 2015,112(6):1232-1242.
|
|
|
| [13] |
Hogwood C E, Tait A S, Koloteva-Levine N , et al. The dynamics of the CHO host cell protein profile during clarification and protein A capture in a platform antibody purification process. Biotechnology and Bioengineering, 2013,110(1):240-251.
doi: 10.1002/bit.24607
|
|
|
| [14] |
Tait A S ,Hogwood C E M,Smales C M,et al. Host cell protein dynamics in the supernatant of a mAb producing CHO cell line. Biotechnology and Bioengineering, 2012,109(4):971-982.
doi: 10.1002/bit.24383
|
|
|
| [15] |
Goey C H ,Tsang J M H,Bell D, et al. Cascading effect in bioprocessing-the impact of mild hypothermia on CHO cell behavior and host cell protein composition. Biotechnology and Bioengineering, 2017,114(12):2771-2781.
|
|
|
| [16] |
Goey C H, Bell D, Kontoravdi C . Mild hypothermic culture conditions affect residual host cell protein composition post-protein A chromatography. mAbs, 2018,10(3):476-487.
|
|
|
| [17] |
Pezzini J, Joucla G, Gantier R , et al. Antibody capture by mixed-mode chromatography:a comprehensive study from determination of optimal purification conditions to identification of contaminating host cell proteins. Journal of Chromatography A, 2011,1218(45):8197-8208.
doi: 10.1016/j.chroma.2011.09.036
|
|
|
| [18] |
Nogal B, Chhiba K, Emery J C . Select host cell proteins coelute with monoclonal antibodies in protein A chromatography. Biotechnology Progress, 2012,28(2):454-458.
doi: 10.1002/btpr.1514
|
|
|
| [19] |
Tarrant R D ,Velez-Suberbie M L,Tait A S, et al.Host cell protein adsorption characteristics during protein A chromatography. Biotechnology Progress, 2012,28(4):1037-1044.
doi: 10.1002/btpr.1581
|
|
|
| [20] |
Zhang Q, Goetze A M, Cui H , et al. Characterization of the co-elution of host cell proteins with monoclonal antibodies during protein A purification. Biotechnology Progress, 2016,32(3):708-717.
|
|
|
| [21] |
Bee J S, Machiesky L M, Peng L , et al. Identification of an IgG CDR sequence contributing to co-purification of the host cell protease cathepsin D. Biotechnology Progress, 2017,33(1):140-145.
|
|
|
| [22] |
Gagnon P, Nian R, Lee J , et al. Nonspecific interactions of chromatin with immunoglobulin G and protein A, and their impact on purification performance. Journal of Chromatography A, 2014,1340(2):68-78.
|
|
|
| [23] |
Gagnon P, Nian R, Yang Y , et al. Non-immunospecific association of immunoglobulin G with chromatin during elution from protein A inflates host contamination, aggregate content,and antibody loss. Journal of Chromatography A, 2015,1408(21):51-60.
|
|
|
| [24] |
Nian R, Gagnon P . Advance chromatin extraction enhances performance and productivity of cation exchange chromatography-based capture of Immunoglobulin G monoclonal antibodies. Journal of Chromatography A, 2016,1453:54-61.
|
|
|
| [25] |
Nian R, Zhang W, Tan L , et al. Advance chromatin extraction improves capture performance of protein A affinity chromatography. Journal of Chromatography A, 2016,1431(29):1-7.
|
|
|
| [26] |
Jin M, Szapiel N, Zhang J , et al. Profiling of host cell proteins by two-dimensional difference gel electrophoresis (2D-DIGE): Implications for downstream process development. Biotechnology and Bioengineering, 2010,105(2):306-316.
|
|
|
| [27] |
Farrell A, Mittermayr S, Morrissey B , et al. Quantitative host cell protein analysis using two dimensional data independent LC-MS(E). Analytical Chemistry, 2015,87(18):9186-9193.
|
|
|
| [28] |
Kreimer S, Gao Y, Ray S , et al. Host cell protein profiling by targeted and untargeted analysis of data independent acquisition mass spectrometry data with parallel reaction monitoring verification. Analytical Chemistry, 2017,89(10):5294-5302.
|
|
|
| [29] |
Chiverton L M, Evans C, Pandhal J , et al. Quantitative definition and monitoring of the host cell protein proteome using iTRAQ - a study of an industrial mAb producing CHO-S cell line. Biotechnology Journal, 2016,11(8):1014-1024.
|
|
|
|
Viewed |
|
|
|
Full text
|
|
|
|
|
Abstract
|
|
|
|
|
Cited |
|
|
|
|
| |
Shared |
|
|
|
|
| |
Discussed |
|
|
|
|
