Modulating cell culture oxidative stress reduces protein glycation and acidic charge variant formation

References

• Aitken M, Kleinrock M. Medicines use and spending in the U.S. A review of 2016 and outlook to 2021. Parsippany (NY): Quintiles IMS Institute; 2017.
   Google Scholar
• Mullard A. 2017. 2016 FDA drug approvals. Nat Rev Drug Discov. 16:73–76. doi:10.1038/nrd.2017.14.
   PubMed Web of Science ®Google Scholar
• Gramer MJ. Product quality considerations for mammalian cell culture process development and manufacturing. In: Zhou W, Kantardjieff A, editors. Mammalian cell cultures for biologics manufacturing. Berlin: Springer; 2013. p. 123-166. doi:10.1007/10_2013_214.
   Google Scholar
• Kelley B. 2009. Industrialization of mAb production technology: the bioprocessing industry at a crossroads. MAbs. 1:443–452. doi:10.4161/mabs.1.5.9448.
   PubMed Web of Science ®Google Scholar
• Du Y, Walsh A, Ehrick R, Xu W, May K, Liu H. 2012. Chromatographic analysis of the acidic and basic species of recombinant monoclonal antibodies. MAbs. 4:578–585. doi:10.4161/mabs.21328.
   PubMed Web of Science ®Google Scholar
• Zhao -Y-Y, Wang N, Liu W-H, Tao W-J, Liu -L-L, Shen Z-D. 2016. Charge variants of an avastin biosimilar isolation, characterization, In Vitro properties and pharmacokinetics in rat. PLoS One. 11:e0151874. doi:10.1371/journal.pone.0151874.
   PubMed Web of Science ®Google Scholar
• Khawli LA, Goswami S, Hutchinson R, Kwong ZW, Yang J, Wang X, Yao Z, Sreedhara A, Cano T, Tesar D, et al. Charge variants in IgG1: isolation, characterization, in vitro binding properties and pharmacokinetics in rats. MAbs. 2010;2:613–624. doi:10.4161/mabs.2.5.13089.
   PubMed Web of Science ®Google Scholar
• Boswell CA, Tesar DB, Mukhyala K, Theil FP, Fielder PJ, Khawli LA. 2010. Effects of charge on antibody tissue distribution and pharmacokinetics. Bioconjug Chem. 21:2153–2163. doi:10.1021/bc100261d.
   PubMed Web of Science ®Google Scholar
• Hintersteiner B, Lingg N, Janzek E, Mutschlechner O, Loibner H, Jungbauer A. 2016. Microheterogeneity of therapeutic monoclonal antibodies is governed by changes in the surface charge of the protein. Biotechnol J. 11:1617–1627. doi:10.1002/biot.201600409.
   PubMed Web of Science ®Google Scholar
• Huang L, Lu J, Wroblewski VJ, Beals JM, Riggin RM. 2005. In vivo deamidation characterization of monoclonal antibody by LC/MS/MS. Anal Chem. 77:1432–1439. doi:10.1021/ac0494174.
   PubMed Web of Science ®Google Scholar
• Alt N, Zhang TY, Motchnik P, Taticek R, Quarmby V, Schlothauer T, Beck H, Emrich T, Harris RJ. 2016. Determination of critical quality attributes for monoclonal antibodies using quality by design principles. Biologicals. 44:291–305. doi:10.1016/j.biologicals.2016.02.005.
   PubMed Web of Science ®Google Scholar
• Liu H, Ponniah G, Zhang H-M, Nowak C, Neill A, Gonzalez-Lopez N, Patel R, Cheng G, Kita AZ, Andrien B. 2014. In vitro and in vivo modifications of recombinant and human IgG antibodies. MAbs. 6:1145–1154. doi:10.4161/mabs.29883.
   PubMed Web of Science ®Google Scholar
• Haberger M, Bomans K, Diepold K, Hook M, Gassner J, Schlothauer T, Zwick A, Spick C, Kepert JF, Hienz B, et al. Assessment of chemical modifications of sites in the CDRs of recombinant antibodies. MAbs. 2014;6:327–339. doi:10.4161/mabs.27876.
   PubMed Web of Science ®Google Scholar
• Chung S, Tian J, Tan Z, Chen J, Lee J, Borys M, Li ZJ. 2018. Industrial bioprocessing perspectives on managing therapeutic protein charge variant profiles. Biotechnol Bioeng. 115:1646–1665. doi:10.1002/bit.v115.7.
   PubMed Web of Science ®Google Scholar
• Mallaney M, Wang SH, Sreedhara A. 2014. Effect of ambient light on monoclonal antibody product quality during small-scale mammalian cell culture process in clear glass bioreactors. Biotechnol Prog. 30:562–570. doi:10.1002/btpr.1920.
   PubMed Web of Science ®Google Scholar
• Horvath B, Mun M, Laird MW. 2010. Characterization of a monoclonal antibody cell culture production process using a quality by design approach. Mol Biotechnol. 45:203–206. doi:10.1007/s12033-010-9267-4.
   PubMed Web of Science ®Google Scholar
• Sf A-A, Yang L, Thompson P, Jiang C, Kandula S, Schilling B, Aa S. 2010. Defining process design space for monoclonal antibody cell culture. Biotechnol Bioeng. 106:894–905. doi:10.1002/bit.22659.
   PubMed Web of Science ®Google Scholar
• Rouiller Y, Périlleux A, Vesin MN, Stettler M, Jordan M, Broly H. 2014. Modulation of mAb quality attributes using microliter scale fed-batch cultures. Biotechnol Prog. 30:571–583. doi:10.1002/btpr.1921.
   PubMed Web of Science ®Google Scholar
• Brunner M, Fricke J, Kroll P, Herwig C. 2017. Investigation of the interactions of critical scale-up parameters (pH, pO2and pCO2) on CHO batch performance and critical quality attributes. Bioprocess Biosyst Eng. 40:251–263. doi:10.1007/s00449-016-1672-z.
   PubMed Web of Science ®Google Scholar
• Xie P, Niu H, Chen X, Zhang X, Miao S, Deng X, Liu X, Tan WS, Zhou Y, Fan L. 2016. Elucidating the effects of pH shift on IgG1 monoclonal antibody acidic charge variant levels in Chinese hamster ovary cell cultures. Appl Microbiol Biotechnol. 100:10343–10353. doi:10.1007/s00253-016-7749-4.
   PubMed Web of Science ®Google Scholar
• Yang WC, Minkler DF, Kshirsagar R, Ryll T, Huang YM. 2016. Concentrated fed-batch cell culture increases manufacturing capacity without additional volumetric capacity. J Biotechnol. 217:1–11. doi:10.1016/j.jbiotec.2015.10.009.
   PubMed Web of Science ®Google Scholar
• Yuk IH, Russell S, Tang Y, Hsu WT, Mauger JB, Aulakh RPS, Luo J, Gawlitzek M, Joly JC. 2015. Effects of copper on CHO cells: cellular requirements and product quality considerations. Biotechnol Prog. 31:226–238. doi:10.1002/btpr.2139.
   PubMed Web of Science ®Google Scholar
• Vijayasankaran N, Varma S, Yang Y, Mun M, Arevalo S, Gawlitzek M, Swartz T, Lim A, Li F, Zhang B, et al. Effect of cell culture medium components on color of formulated monoclonal antibody drug substance. Biotechnol Prog. 2013;29:1270–1277. doi:10.1002/btpr.1772.
   PubMed Web of Science ®Google Scholar
• Trexler-Schmidt M, Sargis S, Chiu J, Sze-Khoo S, Mun M, Kao YH, Laird MW. 2010. Identification and prevention of antibody disulfide bond reduction during cell culture manufacturing. Biotechnol Bioeng. 106:452–461. doi:10.1002/bit.22659.
   PubMed Web of Science ®Google Scholar
• Hazeltine LB, Knueven KM, Zhang Y, Lian Z, Olson DJ, Ouyang A. 2016. Chemically defined media modifications to lower tryptophan oxidation of biopharmaceuticals. Biotechnol Prog. 32:178–188. doi:10.1002/btpr.2196.
   PubMed Web of Science ®Google Scholar
• Luo J, Zhang J, Ren D, Tsai WL, Li F, Amanullah A, Hudson T. 2012. Probing of C-terminal lysine variation in a recombinant monoclonal antibody production using Chinese hamster ovary cells with chemically defined media. Biotechnol Bioeng. 109:2306–2315. doi:10.1002/bit.24510.
   PubMed Web of Science ®Google Scholar
• Chaderjian WB, Chin ET, Harris RJ, Etcheverry TM. 2008. Effect of copper sulfate on performance of a serum-free CHO cell culture process and the level of free thiol in the recombinant antibody expressed. Biotechnol Prog. 21:550–553. doi:10.1021/bp0497029.
   Google Scholar
• Hossler P, Wang M, Mcdermott S, Racicot C, Chemfe K, Zhang Y, Chumsae C, Manuilov A. 2015. Cell culture media supplementation of bioflavonoids for the targeted reduction of acidic species charge variants on recombinant therapeutic proteins. Biotechnol Prog. 31:1039–1052. doi:10.1002/btpr.2139.
   PubMed Web of Science ®Google Scholar
• Yuk IH, Zhang B, Yang Y, Dutina G, Leach KD, Vijayasankaran N, Shen AY, Andersen DC, Snedecor BR, Joly JC. 2011. Controlling glycation of recombinant antibody in fed-batch cell cultures. Biotechnol Bioeng. 108:2600–2610. doi:10.1002/bit.v108.11.
   PubMed Web of Science ®Google Scholar
• Ponniah G, Kita A, Nowak C, Neill A, Kori Y, Rajendran S, Liu H. 2015. Characterization of the acidic species of a monoclonal antibody using weak cation exchange chromatography and LC-MS. Anal Chem. 87:9084–9092. doi:10.1021/acs.analchem.5b02385.
   PubMed Web of Science ®Google Scholar
• Miao S, Xie P, Zou M, Fan L, Liu X, Zhou Y, Zhao L, Ding D, Wang H, Ws T. 2017. Identification of multiple sources of the acidic charge variants in an IgG1 monoclonal antibody. Appl Microbiol Biotechnol. 101:5627–5638. doi:10.1007/s00253-017-8301-x.
   PubMed Web of Science ®Google Scholar
• Ponniah G, Nowak C, Neill A, Liu H. 2017. Characterization of charge variants of a monoclonal antibody using weak anion exchange chromatography at subunit levels. Anal Biochem. 520:49–57. doi:10.1016/j.ab.2016.12.017.
   PubMed Web of Science ®Google Scholar
• Zigler JS, Lepe-Zuniga JL, Vistica B, Gery I. 1985. Analysis of the cytotoxic effects of light-exposed hepes-containing culture medium. Vitr Cell Dev Biol. 21:282–287. doi:10.1007/BF02620943.
   PubMed Web of Science ®Google Scholar
• Wellen KE, Thompson CB. 2010. Cellular metabolic stress: considering how cells respond to nutrient excess. Mol Cell. 40:323–332. doi:10.1016/j.molcel.2010.10.004.
   PubMed Web of Science ®Google Scholar
• Hossler P, Mcdermott S, Racicot C, Fann JCH. 2013. Improvement of mammalian cell culture performance through surfactant enabled concentrated feed media. Biotechnol Prog. 29:1023–1033. doi:10.1002/btpr.1739.
   PubMed Web of Science ®Google Scholar
• Mccoy RE, Costa NA, Morris AE. 2015. Factors that determine stability of highly concentrated chemically defined production media. Biotechnol Prog. 31:493–502. doi:10.1002/btpr.2139.
   PubMed Web of Science ®Google Scholar
• Handlogten MW, Zhu M, Ahuja S. 2018. Intracellular response of CHO cells to oxidative stress and its influence on metabolism and antibody production. Biochem Eng J. 133:12–20. doi:10.1016/j.bej.2018.01.031.
   Web of Science ®Google Scholar
• Sathiyapriya V, Selvaraj N, Nandeesha H, Bobby Z, Agrawal A, Pavithran P. 2007. Enhanced glycation of hemoglobin and plasma proteins is associated with increased lipid peroxide levels in non-diabetic hypertensive subjects. Arch Med Res. 38:822–826. doi:10.1016/j.arcmed.2007.05.008.
   PubMed Web of Science ®Google Scholar
• Selvaraj N, Bobby Z, Sridhar MG. 2008. Oxidative stress: does it play a role in the genesis of early glycated proteins? Med Hypotheses. 70:265–268. doi:10.1016/j.mehy.2007.04.049.
   PubMed Web of Science ®Google Scholar
• Selvaraj N, Bobby Z, Sathiyapriya V. 2006. Effect of lipid peroxides and antioxidants on glycation of hemoglobin: an in vitro study on human erythrocytes. Clin Chim Acta. 366:190–195. doi:10.1016/j.cca.2005.10.002.
   PubMed Web of Science ®Google Scholar
• Lj P, Lu L, Xw X, Ry Z, Zhang Q, Js Z, Hu J, Zk Y, Fh D, Qj C, et al. Value of serum glycated albumin and high-sensitivity C-reactive protein levels in the prediction of presence of coronary artery disease in patients with type 2 diabetes. Cardiovasc Diabetol. 2006;5:1–7. doi:10.1186/1475-2840-5-1.
   PubMed Web of Science ®Google Scholar
• Siddique YH, Ara G, Afzal M. 2012. Estimation of lipid peroxidation induced by hydrogen peroxide in cultured human lymphocytes. Dose-Response. 10:1–10. doi:10.2203/dose-response.10-002.Siddique.
   PubMed Web of Science ®Google Scholar
• Bresgen N, Eckl PM. 2015. Oxidative stress and the homeodynamics of iron metabolism. Biomolecules. 5:808–847. doi:10.3390/biom5020808.
   PubMed Web of Science ®Google Scholar
• Xu W, Barrientos T, Andrews NC. 2013. Iron and Copper in Mitochondrial Diseases. Cell Metab. 17:319–328. doi:10.1016/j.cmet.2013.02.004.
   PubMed Web of Science ®Google Scholar
• Bai Y, Wu C, Zhao J, Liu Y-H, Ding W, Ling WLW. 2010. Role of iron and sodium citrate in animal protein-free CHO cell culture medium on cell growth and monoclonal antibody production. Biotechnol Prog. 27:209–219. doi:10.1002/btpr.513.
   PubMed Web of Science ®Google Scholar
• Xu J, Rehmann MS, Xu X, Huang C, Tian J, Qian N-X, Li ZJ. Improving titer while maintaining quality of final formulated drug substance via optimization of CHO cell culture conditions in low-iron chemically defined media. In: mAbs. Taylor & Francis; 2018. doi:10.1080/19420862.2018.1433978.
   Google Scholar
• Xu J, Jin M, Song H, Huang C, Xu X, Tian J, Qian NX, Steger K, Lewen NS, Tao L, et al. Brown drug substance color investigation in cell culture manufacturing using chemically defined media: A case study. Process Biochem. 2014;49:130–139. doi:10.1016/j.procbio.2013.10.015.
   Web of Science ®Google Scholar
• Zhang Y, Wang Z, Li X, Wang L, Yin M, Wang L, Chen N, Fan C, Song H. 2016. Dietary Iron oxide nanoparticles delay aging and ameliorate neurodegeneration in drosophila. Adv Mater. 28:1387–1393. doi:10.1002/adma.v28.7.
   PubMed Web of Science ®Google Scholar
• Erkan N, Ayranci G, Ayranci E. 2008. Antioxidant activities of rosemary (Rosmarinus Officinalis L.) extract, blackseed (Nigella sativa L.) essential oil, carnosic acid, rosmarinic acid and sesamol. Food Chem. 110:76–82. doi:10.1016/j.foodchem.2008.01.058.
   PubMed Web of Science ®Google Scholar
• Long LH, Hoi A, Halliwell B. 2010. Instability of, and generation of hydrogen peroxide by, phenolic compounds in cell culture media. Arch Biochem Biophys. 501:162–169. doi:10.1016/j.abb.2010.06.012.
   PubMed Web of Science ®Google Scholar
• Kim H-S, Quon MJ, Kim J. 2014. New insights into the mechanisms of polyphenols beyond antioxidant properties; lessons from the green tea polyphenol, epigallocatechin 3-gallate. Redox Biol. 2:187–195. doi:10.1016/j.redox.2013.12.022.
   PubMed Web of Science ®Google Scholar
• Davies MJ. 2016. Protein oxidation and peroxidation. Biochem J. 473:805–825. doi:10.1042/BJ20151227.
   PubMed Web of Science ®Google Scholar
• Gebicki S, Gebicki JM. 1993. Formation of peroxides in amino-acids and proteins exposed to oxygen free-radicals. Biochem J. 289:743–749. doi:10.1042/bj2890743.
   PubMed Web of Science ®Google Scholar
• Debski D, Smulik R, Zielonka J, Michałowski B, Jakubowska M, Debowska K, Adamus J, Marcinek A, Kalyanaraman B, Sikora A. 2016. Mechanism of oxidative conversion of Amplex® Red to resorufin: pulse radiolysis and enzymatic studies. Free Radic Biol Med. 95:323–332. doi:10.1016/j.freeradbiomed.2016.03.027.
   PubMed Web of Science ®Google Scholar