Repressing expression of difficult‐to‐express recombinant proteins during the selection process increases productivity of CHO stable pools
NRC publication: Yes
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| Published in: | Biotechnology and bioengineering Vol. 120; no. 10; pp. 2840 - 2852 |
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| Main Authors: | , , , , , |
| Format: | Journal Article |
| Language: | English |
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United States
Wiley
01.10.2023
Wiley Subscription Services, Inc |
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| ISSN: | 1097-0290, 0006-3592, 1097-0290 |
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| Abstract | NRC publication: Yes More than half of licensed therapeutic recombinant proteins (r‐proteins) are manufac-tured using constitutively‐expressing, stably‐transfected Chinese hamster ovary (CHO)clones. While constitutive CHO expression systems have proven their efficacy for themanufacturing of monoclonal antibodies, many next‐generation therapeutics such ascytokines and bispecific antibodies as well as biological targets such as ectodomains oftransmembrane receptors remain intrinsically challenging to produce. Herein, weexploited a cumate‐inducible CHO platform allowing reduced expression of variousclasses of r‐proteins during selection of stable pools. Following stable pool generation,fed‐batch productions showed that pools generated without cumate (OFF‐pools) weresignificantly more productive than pools selected in the presence of cumate (ON‐pools)for 8 out of the 10 r‐proteins tested, including cytokines, G‐protein coupled receptors(GPCRs), the HVEM membrane receptor ectodomain, the multifunctional protein HighMobility Group protein B1 (HMGB1), as well as monoclonal and bispecific T‐cell engagerantibodies. We showed that OFF‐pools contain a significantly larger proportion of cellsproducing high levels of r‐proteins and that these cells tend to proliferate faster whenexpression is turned off, suggesting that r‐protein overexpression imposes a metabolicburden on the cells. Cell viability was lower and pool recovery was delayed duringselection of ON‐pools (mimicking constitutive expression), suggesting that high producerswere likely lost or overgrown by faster‐growing, low‐producing cells. We also observed acorrelation between the expression levels of the GPCRs with Binding immunoglobulinProtein, an endoplasmic reticulum (ER) stress marker. Taken together, these data suggestthat using an inducible system to minimize r‐protein expression during stable CHO poolselection reduces cellular stresses, including ER stress and metabolic burden, leading topools with greater frequency of high‐expressing cells, resulting in improved volumetricproductivity. |
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| AbstractList | More than half of licensed therapeutic recombinant proteins (r‐proteins) are manufactured using constitutively‐expressing, stably‐transfected Chinese hamster ovary (CHO) clones. While constitutive CHO expression systems have proven their efficacy for the manufacturing of monoclonal antibodies, many next‐generation therapeutics such as cytokines and bispecific antibodies as well as biological targets such as ectodomains of transmembrane receptors remain intrinsically challenging to produce. Herein, we exploited a cumate‐inducible CHO platform allowing reduced expression of various classes of r‐proteins during selection of stable pools. Following stable pool generation, fed‐batch productions showed that pools generated without cumate (OFF‐pools) were significantly more productive than pools selected in the presence of cumate (ON‐pools) for 8 out of the 10 r‐proteins tested, including cytokines, G‐protein coupled receptors (GPCRs), the HVEM membrane receptor ectodomain, the multifunctional protein High Mobility Group protein B1 (HMGB1), as well as monoclonal and bispecific T‐cell engager antibodies. We showed that OFF‐pools contain a significantly larger proportion of cells producing high levels of r‐proteins and that these cells tend to proliferate faster when expression is turned off, suggesting that r‐protein overexpression imposes a metabolic burden on the cells. Cell viability was lower and pool recovery was delayed during selection of ON‐pools (mimicking constitutive expression), suggesting that high producers were likely lost or overgrown by faster‐growing, low‐producing cells. We also observed a correlation between the expression levels of the GPCRs with Binding immunoglobulin Protein, an endoplasmic reticulum (ER) stress marker. Taken together, these data suggest that using an inducible system to minimize r‐protein expression during stable CHO pool selection reduces cellular stresses, including ER stress and metabolic burden, leading to pools with greater frequency of high‐expressing cells, resulting in improved volumetric productivity. More than half of licensed therapeutic recombinant proteins (r-proteins) are manufactured using constitutively-expressing, stably-transfected Chinese hamster ovary (CHO) clones. While constitutive CHO expression systems have proven their efficacy for the manufacturing of monoclonal antibodies, many next-generation therapeutics such as cytokines and bispecific antibodies as well as biological targets such as ectodomains of transmembrane receptors remain intrinsically challenging to produce. Herein, we exploited a cumate-inducible CHO platform allowing reduced expression of various classes of r-proteins during selection of stable pools. Following stable pool generation, fed-batch productions showed that pools generated without cumate (OFF-pools) were significantly more productive than pools selected in the presence of cumate (ON-pools) for 8 out of the 10 r-proteins tested, including cytokines, G-protein coupled receptors (GPCRs), the HVEM membrane receptor ectodomain, the multifunctional protein High Mobility Group protein B1 (HMGB1), as well as monoclonal and bispecific T-cell engager antibodies. We showed that OFF-pools contain a significantly larger proportion of cells producing high levels of r-proteins and that these cells tend to proliferate faster when expression is turned off, suggesting that r-protein overexpression imposes a metabolic burden on the cells. Cell viability was lower and pool recovery was delayed during selection of ON-pools (mimicking constitutive expression), suggesting that high producers were likely lost or overgrown by faster-growing, low-producing cells. We also observed a correlation between the expression levels of the GPCRs with Binding immunoglobulin Protein, an endoplasmic reticulum (ER) stress marker. Taken together, these data suggest that using an inducible system to minimize r-protein expression during stable CHO pool selection reduces cellular stresses, including ER stress and metabolic burden, leading to pools with greater frequency of high-expressing cells, resulting in improved volumetric productivity. NRC publication: Yes More than half of licensed therapeutic recombinant proteins (r-proteins) are manufactured using constitutively-expressing, stably-transfected Chinese hamster ovary (CHO) clones. While constitutive CHO expression systems have proven their efficacy for the manufacturing of monoclonal antibodies, many next-generation therapeutics such as cytokines and bispecific antibodies as well as biological targets such as ectodomains of transmembrane receptors remain intrinsically challenging to produce. Herein, we exploited a cumate-inducible CHO platform allowing reduced expression of various classes of r-proteins during selection of stable pools. Following stable pool generation, fed-batch productions showed that pools generated without cumate (OFF-pools) were significantly more productive than pools selected in the presence of cumate (ON-pools) for 8 out of the 10 r-proteins tested, including cytokines, G-protein coupled receptors (GPCRs), the HVEM membrane receptor ectodomain, the multifunctional protein High Mobility Group protein B1 (HMGB1), as well as monoclonal and bispecific T-cell engager antibodies. We showed that OFF-pools contain a significantly larger proportion of cells producing high levels of r-proteins and that these cells tend to proliferate faster when expression is turned off, suggesting that r-protein overexpression imposes a metabolic burden on the cells. Cell viability was lower and pool recovery was delayed during selection of ON-pools (mimicking constitutive expression), suggesting that high producers were likely lost or overgrown by faster-growing, low-producing cells. We also observed a correlation between the expression levels of the GPCRs with Binding immunoglobulin Protein, an endoplasmic reticulum (ER) stress marker. Taken together, these data suggest that using an inducible system to minimize r-protein expression during stable CHO pool selection reduces cellular stresses, including ER stress and metabolic burden, leading to pools with greater frequency of high-expressing cells, resulting in improved volumetric productivity.More than half of licensed therapeutic recombinant proteins (r-proteins) are manufactured using constitutively-expressing, stably-transfected Chinese hamster ovary (CHO) clones. While constitutive CHO expression systems have proven their efficacy for the manufacturing of monoclonal antibodies, many next-generation therapeutics such as cytokines and bispecific antibodies as well as biological targets such as ectodomains of transmembrane receptors remain intrinsically challenging to produce. Herein, we exploited a cumate-inducible CHO platform allowing reduced expression of various classes of r-proteins during selection of stable pools. Following stable pool generation, fed-batch productions showed that pools generated without cumate (OFF-pools) were significantly more productive than pools selected in the presence of cumate (ON-pools) for 8 out of the 10 r-proteins tested, including cytokines, G-protein coupled receptors (GPCRs), the HVEM membrane receptor ectodomain, the multifunctional protein High Mobility Group protein B1 (HMGB1), as well as monoclonal and bispecific T-cell engager antibodies. We showed that OFF-pools contain a significantly larger proportion of cells producing high levels of r-proteins and that these cells tend to proliferate faster when expression is turned off, suggesting that r-protein overexpression imposes a metabolic burden on the cells. Cell viability was lower and pool recovery was delayed during selection of ON-pools (mimicking constitutive expression), suggesting that high producers were likely lost or overgrown by faster-growing, low-producing cells. We also observed a correlation between the expression levels of the GPCRs with Binding immunoglobulin Protein, an endoplasmic reticulum (ER) stress marker. Taken together, these data suggest that using an inducible system to minimize r-protein expression during stable CHO pool selection reduces cellular stresses, including ER stress and metabolic burden, leading to pools with greater frequency of high-expressing cells, resulting in improved volumetric productivity. |
| Author | Stuible, Matthew Durocher, Yves Lord Dufour, Simon Loignon, Martin Maltais, Jean‐Sébastien Morasse, Audrey |
| Author_xml | – sequence: 1 fullname: Maltais, Jean‐Sébastien – sequence: 2 fullname: Lord Dufour, Simon – sequence: 3 fullname: Morasse, Audrey – sequence: 4 fullname: Stuible, Matthew – sequence: 5 fullname: Loignon, Martin – sequence: 6 fullname: Durocher, Yves |
| BackLink | https://www.ncbi.nlm.nih.gov/pubmed/37232536$$D View this record in MEDLINE/PubMed |
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| CitedBy_id | crossref_primary_10_1016_j_jbiotec_2024_04_017 crossref_primary_10_1002_biot_70079 crossref_primary_10_1093_nar_gkaf546 crossref_primary_10_1093_nar_gkaf732 crossref_primary_10_1002_btpr_70029 crossref_primary_10_1007_s10529_025_03573_9 crossref_primary_10_1016_j_nbt_2025_04_011 crossref_primary_10_1016_j_ijbiomac_2025_144695 |
| Cites_doi | 10.1016/S0959-8049(94)00401-3 10.1016/j.biotechadv.2021.107831 10.1110/ps.051489405 10.1038/ncb0311-184 10.1002/bit.26280 10.1016/j.biotechadv.2011.08.022 10.1371/journal.pone.0183694 10.1073/pnas.89.12.5547 10.1182/blood-2008-12-189266 10.1007/s11095-010-0172-0 10.1007/s10529-014-1537-y 10.1002/btpr.2495 10.1002/btpr.2772 10.3390/ph6050579 10.1016/j.jbiotec.2017.04.028 10.2174/138920110791111960 10.1016/J.JBIOTEC.2022.03.010 10.1002/bit.25687 10.1007/s10616-006-9041-4 10.1016/j.ymben.2012.12.003 10.3390/pr5020020 10.1016/j.imlet.2017.08.010 10.1002/bit.28387 10.3389/fimmu.2020.615603 10.3390/ANTIB8030043 10.1002/btpr.2572 10.3389/fonc.2017.00078 10.1080/19420862.2021.2005507 10.1002/btpr.2548 10.1002/bit.28127 10.1002/btpr.3186 10.1089/ars.2009.2485 10.3389/FBIOE.2021.658325 10.1016/j.biotechadv.2020.107552 10.1016/j.ejpb.2011.01.005 10.1016/J.COCHE.2018.09.010 10.1002/btpr.2467 10.1002/btpr.9 10.1002/bit.22723 10.1007/s10616-005-3765-4 10.1002/btpr.2839 10.1002/btpr.2493 10.1038/sj.embor.7400779 10.1186/1472-6750-6-43 10.1016/J.JBIOTEC.2019.03.009 10.1002/bit.25116 10.1007/s10529-009-0050-1 10.1124/jpet.108.138263 10.1016/J.BBAMCR.2013.06.028 10.1002/bit.20566 10.1016/j.jbiotec.2017.06.009 10.1002/btpr.2439 10.1002/BIT.27995 10.1016/j.ddtec.2021.02.003 10.1016/j.copbio.2009.10.008 |
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| Keywords | ER stress difficult-to-express protein inducible expression cumate productivity CHO cells |
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| References | e_1_2_9_31_1 e_1_2_9_52_1 e_1_2_9_50_1 e_1_2_9_10_1 e_1_2_9_35_1 e_1_2_9_56_1 e_1_2_9_12_1 e_1_2_9_33_1 e_1_2_9_54_1 e_1_2_9_14_1 e_1_2_9_39_1 e_1_2_9_16_1 e_1_2_9_37_1 e_1_2_9_58_1 e_1_2_9_18_1 e_1_2_9_41_1 e_1_2_9_20_1 e_1_2_9_22_1 e_1_2_9_45_1 e_1_2_9_24_1 e_1_2_9_43_1 e_1_2_9_8_1 e_1_2_9_6_1 Pedrazzoli P. (e_1_2_9_32_1) 1996; 16 e_1_2_9_4_1 e_1_2_9_2_1 Nims R. W. (e_1_2_9_27_1) 2006; 123 e_1_2_9_26_1 e_1_2_9_49_1 e_1_2_9_47_1 Nissen C. (e_1_2_9_28_1) 1994; 30 e_1_2_9_30_1 e_1_2_9_53_1 e_1_2_9_51_1 e_1_2_9_11_1 e_1_2_9_34_1 e_1_2_9_57_1 e_1_2_9_13_1 e_1_2_9_55_1 Querol S. (e_1_2_9_36_1) 1999; 84 e_1_2_9_15_1 e_1_2_9_38_1 e_1_2_9_17_1 e_1_2_9_59_1 e_1_2_9_19_1 e_1_2_9_42_1 e_1_2_9_40_1 e_1_2_9_21_1 e_1_2_9_46_1 e_1_2_9_23_1 e_1_2_9_44_1 e_1_2_9_7_1 e_1_2_9_5_1 e_1_2_9_3_1 e_1_2_9_9_1 e_1_2_9_25_1 e_1_2_9_27_2 e_1_2_9_48_1 e_1_2_9_29_1 |
| References_xml | – volume: 30 start-page: S12 issue: 3 year: 1994 ident: e_1_2_9_28_1 article-title: Glycosylation of recombinant human granulocyte colony stimulating factor: Implications for stability and potency publication-title: European Journal of Cancer (Oxford, England: 1990) doi: 10.1016/S0959-8049(94)00401-3 – ident: e_1_2_9_14_1 doi: 10.1016/j.biotechadv.2021.107831 – ident: e_1_2_9_38_1 doi: 10.1110/ps.051489405 – ident: e_1_2_9_47_1 doi: 10.1038/ncb0311-184 – ident: e_1_2_9_12_1 doi: 10.1002/bit.26280 – ident: e_1_2_9_59_1 doi: 10.1016/j.biotechadv.2011.08.022 – ident: e_1_2_9_40_1 doi: 10.1371/journal.pone.0183694 – ident: e_1_2_9_13_1 doi: 10.1073/pnas.89.12.5547 – ident: e_1_2_9_3_1 doi: 10.1182/blood-2008-12-189266 – ident: e_1_2_9_51_1 doi: 10.1007/s11095-010-0172-0 – ident: e_1_2_9_16_1 doi: 10.1007/s10529-014-1537-y – ident: e_1_2_9_37_1 doi: 10.1002/btpr.2495 – ident: e_1_2_9_48_1 doi: 10.1002/btpr.2772 – ident: e_1_2_9_21_1 doi: 10.3390/ph6050579 – volume: 123 start-page: 153 year: 2006 ident: e_1_2_9_27_1 article-title: Detection of adventitious viruses in biologicals—A rare occurrence publication-title: Developments in Biologicals – ident: e_1_2_9_22_1 doi: 10.1016/j.jbiotec.2017.04.028 – ident: e_1_2_9_30_1 doi: 10.2174/138920110791111960 – ident: e_1_2_9_43_1 doi: 10.1016/J.JBIOTEC.2022.03.010 – ident: e_1_2_9_17_1 doi: 10.1002/bit.25687 – ident: e_1_2_9_11_1 doi: 10.1007/s10616-006-9041-4 – ident: e_1_2_9_24_1 doi: 10.1016/j.ymben.2012.12.003 – ident: e_1_2_9_55_1 doi: 10.3390/pr5020020 – ident: e_1_2_9_39_1 doi: 10.1016/j.imlet.2017.08.010 – volume: 84 start-page: 493 issue: 6 year: 1999 ident: e_1_2_9_36_1 article-title: Effect of glycosylation of recombinant human granulocytic colony‐stimulating factor on expansion cultures of umbilical cord blood CD34+ cells publication-title: Haematologica – ident: e_1_2_9_20_1 doi: 10.1002/bit.28387 – ident: e_1_2_9_57_1 doi: 10.3389/fimmu.2020.615603 – ident: e_1_2_9_53_1 doi: 10.3390/ANTIB8030043 – ident: e_1_2_9_26_1 doi: 10.1002/btpr.2572 – ident: e_1_2_9_6_1 doi: 10.3389/fonc.2017.00078 – ident: e_1_2_9_56_1 doi: 10.1080/19420862.2021.2005507 – ident: e_1_2_9_54_1 doi: 10.1002/btpr.2548 – ident: e_1_2_9_19_1 doi: 10.1002/bit.28127 – ident: e_1_2_9_58_1 doi: 10.1002/btpr.3186 – ident: e_1_2_9_52_1 doi: 10.1089/ars.2009.2485 – ident: e_1_2_9_9_1 doi: 10.3389/FBIOE.2021.658325 – ident: e_1_2_9_27_2 – ident: e_1_2_9_29_1 doi: 10.1016/j.biotechadv.2020.107552 – ident: e_1_2_9_7_1 doi: 10.1016/j.ejpb.2011.01.005 – ident: e_1_2_9_44_1 doi: 10.1016/J.COCHE.2018.09.010 – ident: e_1_2_9_15_1 doi: 10.1002/btpr.2467 – ident: e_1_2_9_45_1 doi: 10.1002/btpr.9 – ident: e_1_2_9_5_1 doi: 10.1002/bit.22723 – ident: e_1_2_9_49_1 doi: 10.1007/s10616-005-3765-4 – ident: e_1_2_9_31_1 doi: 10.1002/btpr.2839 – ident: e_1_2_9_42_1 doi: 10.1002/btpr.2493 – ident: e_1_2_9_46_1 doi: 10.1038/sj.embor.7400779 – volume: 16 start-page: 1781 issue: 4 year: 1996 ident: e_1_2_9_32_1 article-title: Effects of glycosylated and non‐glycosylated G‐CSFs, alone and in combination with other cytokines, on the growth of human progenitor cells publication-title: Anticancer Research – ident: e_1_2_9_25_1 doi: 10.1186/1472-6750-6-43 – ident: e_1_2_9_33_1 doi: 10.1016/J.JBIOTEC.2019.03.009 – ident: e_1_2_9_35_1 doi: 10.1002/bit.25116 – ident: e_1_2_9_4_1 doi: 10.1007/s10529-009-0050-1 – ident: e_1_2_9_8_1 doi: 10.1124/jpet.108.138263 – ident: e_1_2_9_41_1 doi: 10.1016/J.BBAMCR.2013.06.028 – ident: e_1_2_9_18_1 doi: 10.1002/bit.20566 – ident: e_1_2_9_34_1 doi: 10.1016/j.jbiotec.2017.06.009 – ident: e_1_2_9_23_1 doi: 10.1002/btpr.2439 – ident: e_1_2_9_2_1 doi: 10.1002/BIT.27995 – ident: e_1_2_9_50_1 doi: 10.1016/j.ddtec.2021.02.003 – ident: e_1_2_9_10_1 doi: 10.1016/j.copbio.2009.10.008 |
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| Snippet | NRC publication: Yes More than half of licensed therapeutic recombinant proteins (r‐proteins) are manufactured using constitutively‐expressing, stably‐transfected Chinese hamster... More than half of licensed therapeutic recombinant proteins (r-proteins) are manufactured using constitutively-expressing, stably-transfected Chinese hamster... |
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| SubjectTerms | Antibodies Bispecific antibodies Cell surface receptors Cell viability Cellular stress response CHO cells cumate Cytokines difficult‐to‐express protein Endoplasmic reticulum ER stress High mobility group proteins HMGB1 protein inducible expression Metabolism Monoclonal antibodies produc Productivity Proteins Receptors |
| Title | Repressing expression of difficult‐to‐express recombinant proteins during the selection process increases productivity of CHO stable pools |
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