Abstract
Chinese hamster ovary cells are the main expression system for recombinant therapeutic proteins. During the production of these proteins, certain host cell proteins are secreted, broken down, and released by host cells in the culture along with the proteins of interest. These host cell proteins are often difficult to remove during the downstream purification process, and thus affect the quality, safety, and effectiveness of recombinant protein biopharmaceutical products and increase the production cost of recombinant therapeutic proteins. Therefore, host cell protein production must be reduced as much as possible during the production process and eliminated during purification. This article reviews the harm caused by host cell proteins in the production of recombinant protein drugs using Chinese hamster ovary cell, factors affecting host cell proteins, the monitoring and identification of these proteins, and methods to reduce their type and quantity in the final product.
Graphical Abstract
[http://dx.doi.org/10.3389/fbioe.2022.880155] [PMID: 35860329]
[PMID: 35658884]
[http://dx.doi.org/10.1016/j.jbiotec.2021.06.019] [PMID: 34171439]
[http://dx.doi.org/10.1002/btpr.1948] [PMID: 25044920]
[http://dx.doi.org/10.1002/bit.26360] [PMID: 28627725]
[http://dx.doi.org/10.1016/j.jpba.2019.06.021] [PMID: 31234041]
[http://dx.doi.org/10.1002/biot.202200115] [PMID: 36427352]
[http://dx.doi.org/10.1208/s12248-016-9998-7] [PMID: 27739010]
[http://dx.doi.org/10.1002/btpr.2640] [PMID: 29693803]
[http://dx.doi.org/10.1002/btpr.3128] [PMID: 33476097]
[http://dx.doi.org/10.1002/biot.201500550] [PMID: 27214759]
[http://dx.doi.org/10.1007/978-1-4939-6972-2_8] [PMID: 28493127]
[http://dx.doi.org/10.1016/j.pep.2017.04.006] [PMID: 28414067]
[http://dx.doi.org/10.1371/journal.pone.0265886] [PMID: 35320326]
[http://dx.doi.org/10.1016/j.ymben.2021.04.004] [PMID: 33887460]
[http://dx.doi.org/10.1002/bit.26437] [PMID: 28843000]
[http://dx.doi.org/10.1002/btpr.2820] [PMID: 30972970]
[http://dx.doi.org/10.1021/acs.analchem.8b01236] [PMID: 30048127]
[http://dx.doi.org/10.1002/btpr.2455] [PMID: 28249362]
[http://dx.doi.org/10.1002/btpr.2788] [PMID: 30767403]
[http://dx.doi.org/10.1002/bit.25615] [PMID: 25894672]
[http://dx.doi.org/10.1002/bit.22532] [PMID: 19739084]
[http://dx.doi.org/10.1002/btpr.3224] [PMID: 34751518]
[http://dx.doi.org/10.1002/bit.28128] [PMID: 35508759]
[http://dx.doi.org/10.1002/0471140864.ps0601s80]
[http://dx.doi.org/10.1016/j.chroma.2020.461237] [PMID: 32709313]
[http://dx.doi.org/10.2144/btn-2020-0074] [PMID: 32615786]
[http://dx.doi.org/10.1002/btpr.2936] [PMID: 31661608]
[http://dx.doi.org/10.1002/btpr.2150] [PMID: 26259961]
[http://dx.doi.org/10.1002/btpr.2397] [PMID: 27798957]
[http://dx.doi.org/10.1038/srep44246] [PMID: 28281648]
[http://dx.doi.org/10.1021/acs.molpharmaceut.0c00794] [PMID: 32941040]
[http://dx.doi.org/10.1016/j.ejpb.2020.05.017] [PMID: 32445968]
[http://dx.doi.org/10.1002/btpr.2732] [PMID: 30320962]
[http://dx.doi.org/10.1016/j.chroma.2016.01.047] [PMID: 26896920]
[http://dx.doi.org/10.1016/j.xphs.2016.02.022] [PMID: 27056628]
[http://dx.doi.org/10.1021/acs.analchem.1c00042] [PMID: 34032423]
[http://dx.doi.org/10.1007/s11095-021-03160-3] [PMID: 34981317]
[http://dx.doi.org/10.1080/19420862.2021.1955811] [PMID: 34365906]
[http://dx.doi.org/10.1002/biot.201200018] [PMID: 23436780]
[http://dx.doi.org/10.1007/978-1-4939-6972-2_16] [PMID: 28493135]
[http://dx.doi.org/10.1007/978-1-4939-7268-5_1] [PMID: 29019120]
[http://dx.doi.org/10.1371/journal.pone.0223840] [PMID: 31622403]
[http://dx.doi.org/10.1155/2015/454256] [PMID: 25667921]
[http://dx.doi.org/10.1002/prca.201400119] [PMID: 25400138]
[http://dx.doi.org/10.1016/j.ab.2020.113972] [PMID: 32979367]
[http://dx.doi.org/10.1021/acs.analchem.5b01377] [PMID: 26280711]
[http://dx.doi.org/10.1021/acs.analchem.7b00304] [PMID: 28414239]
[http://dx.doi.org/10.1002/bit.25882] [PMID: 26550778]
[http://dx.doi.org/10.1016/j.xphs.2021.08.024] [PMID: 34461112]
[http://dx.doi.org/10.1021/acs.analchem.0c01175] [PMID: 32628830]
[http://dx.doi.org/10.1016/j.jpba.2020.113256] [PMID: 32229402]
[http://dx.doi.org/10.1021/acs.analchem.9b03952] [PMID: 31860266]
[http://dx.doi.org/10.1002/bit.27514] [PMID: 32706388]
[http://dx.doi.org/10.1002/bit.27635] [PMID: 33241851]
[http://dx.doi.org/10.1002/btpr.3244] [PMID: 35150475]
[http://dx.doi.org/10.1080/19420862.2021.1955432] [PMID: 34347561]
[http://dx.doi.org/10.1016/j.jpba.2021.114069] [PMID: 33901758]
[http://dx.doi.org/10.1021/acs.analchem.9b05081] [PMID: 31999105]
[http://dx.doi.org/10.1016/j.xphs.2021.06.033] [PMID: 34224732]
[http://dx.doi.org/10.1002/bit.25286] [PMID: 24888712]
[http://dx.doi.org/10.1021/acs.jproteome.0c00664] [PMID: 33016074]
[http://dx.doi.org/10.1002/bit.27808] [PMID: 33930190]
[http://dx.doi.org/10.1016/j.biotechadv.2018.03.021] [PMID: 29654903]
[http://dx.doi.org/10.1002/bit.27857] [PMID: 34125434]
[http://dx.doi.org/10.1002/bit.26731] [PMID: 29777593]
[http://dx.doi.org/10.1002/bit.26237] [PMID: 27943242]
[http://dx.doi.org/10.1038/s41467-020-15866-w] [PMID: 32313013]
[http://dx.doi.org/10.1002/bit.27513] [PMID: 32706389]
[http://dx.doi.org/10.1016/j.pep.2019.02.016] [PMID: 30825515]
[http://dx.doi.org/10.1016/j.pep.2019.105460] [PMID: 31351123]
[http://dx.doi.org/10.1016/j.chroma.2022.463385] [PMID: 35933770]
[http://dx.doi.org/10.1016/j.jbiotec.2019.08.013] [PMID: 31442501]
[http://dx.doi.org/10.1002/btpr.2272] [PMID: 27073178]
[http://dx.doi.org/10.1002/bit.27213] [PMID: 31654407]
[http://dx.doi.org/10.1016/j.chroma.2019.02.056] [PMID: 30898377]
[http://dx.doi.org/10.1016/j.ymben.2018.11.007] [PMID: 30468874]