Bioprocessing of mAb (Monoclonal Antibodies) using Chinese Hamster Ovary (CHO) Cells: A Review

  • Richelle Bertly Josefano Institut Bio Scientia Internasional Indonesia
  • Aivyanca A Institut Bio Scientia Internasional Indonesia
  • Charlivo Mikaichi Dungus Institut Bio Scientia Internasional Indonesia
  • Jason Jonathan Hamid Institut Bio Scientia Internasional Indonesia
  • Katherine Katherine Institut Bio Scientia Internasional Indonesia https://orcid.org/0000-0002-3020-6996
Keywords: Monoclonal antibodies, Bioprocessing process, Chinese hamster ovary (CHO) cells, Upstream prcoess, Downstream process

Abstract

Monoclonal antibodies (mAb) are known to be able to be produced from Chinese Hamster Ovary (CHO) cells. It has become increasingly important throughout the years due to its efficiency and revolutionary treatment for various diseases such as cancer, autoimmune diseases, and so forth. This review examines several upstream and downstream processes involved in the production of mAb including CHO cell maintenance, cellular engineering of CHO, transfection of plasmids into CHO cells, clonal selection and screening, culture of rCHO cells, cell harvesting, purification, and polishing. Several challenges of the bioprocessing process include a lack of large up scaling for industrial purposes, high capital costs, as well as productivity inefficiencies. However, a solution proposed is for biopharmaceutical companies to research further into the downstream processing for a continuous, efficient, and productive process.

Downloads

Download data is not yet available.

Author Biographies

Richelle Bertly Josefano, Institut Bio Scientia Internasional Indonesia

Department of Biotechnology, Institut Bio Scientia Internasional Indonesia, Jakarta, Indonesia

Aivyanca A, Institut Bio Scientia Internasional Indonesia

Department of Biotechnology, Institut Bio Scientia Internasional Indonesia, Jakarta, Indonesia

Charlivo Mikaichi Dungus, Institut Bio Scientia Internasional Indonesia

Department of Biotechnology, Institut Bio Scientia Internasional Indonesia, Jakarta, Indonesia

Jason Jonathan Hamid, Institut Bio Scientia Internasional Indonesia

Department of Biotechnology, Institut Bio Scientia Internasional Indonesia, Jakarta, Indonesia

Katherine Katherine, Institut Bio Scientia Internasional Indonesia

Department of Biotechnology, Institut Bio Scientia Internasional Indonesia, Jakarta, Indonesia

References

Ahmadi, S., Davami, F., Davoudi, N., Nematpour, F., Ahmadi, M., Ebadat, S., Azadmanesh, K., Barkhordari, F., & Mahboudi, F. (2017). Monoclonal antibodies expression improvement in CHO cells by Piggybac transposition regarding vectors ratios and design. PLOS ONE, 12(6). https://doi.org/10.1371/journal.pone.0179902
Alhuthali, S., Kotidis, P., & Kontoravdi, C. (2021). Osmolality effects on Cho cell growth, cell volume, antibody productivity and glycosylation. International Journal of Molecular Sciences, 22(7), 3290. https://doi.org/10.3390/ijms22073290
Alhajj, M., & Farhana, A. (2022). Enzyme linked immunosorbent assay. Retrieved on March 14, 2022, from https://www.ncbi.nlm.nih.gov/books/NBK555922/
Almagro, J. C., Daniels-Wells, T. R., Perez-Tapia, S. M., & Penichet, M. L. (2018). Progress and challenges in the design and clinical development of antibodies for cancer therapy. Frontiers in Immunology, 8. https://doi.org/10.3389/fimmu.2017.01751
Ambrožič, R., Arzenšek, D., & Podgornik, A. (2020). Designing scalable ultrafiltration/diafiltration process of monoclonal antibodies via mathematical modeling by coupling mass balances and Poisson–Boltzmann equation. Biotechnology and Bioengineering, 118(2), 633–646. https://doi.org/10.1002/bit.27598
Bayat, H., Hoseinzadeh, S., Pourmaleki, E., Ahani, R., & Rahimpour, A. (2018). Evaluation of different vector design strategies for the expression of recombinant monoclonal antibodies in CHO Cells. Preparative Biochemistry & Biotechnology, 48(2), 160–164. https://doi.org/10.1080/10826068.2017.1421966
Baek, Y., Yang, D., & Zydney, A. L. (2018). Development of a hydrodynamic cleaning cycle for ultrafiltration/diafiltration processes used for monoclonal antibody formulation. Industrial & Engineering Chemistry Research. https://doi.org/10.1021/acs.iecr.8b02608
Batra, J., & Rathore, A. S. (2016). Glycosylation of monoclonal antibody products: Current status and future prospects. Biotechnology Progress, 32(5), 1091–1102. https://doi.org/10.1002/btpr.2366
Bhatia, S., & Bera, T. (2015). Classical and nonclassical techniques for secondary metabolite production in plant cell culture. Modern Applications of Plant Biotechnology in Pharmaceutical Sciences, 231–291. https://doi.org/10.1016/b978-0-12-802221-4.00007-8

Biechele, P., Busse, C., Solle, D., Scheper, T., & Reardon, K. (2015). Sensor Systems for Bioprocess Monitoring. Engineering in Life Sciences, 15(5), 469–488. https://doi.org/10.1002/elsc.201500014

Bielser, J. M., Wolf, M., Souquet, J., Broly, H., & Morbidelli, M. (2018). Perfusion mammalian cell culture for recombinant protein manufacturing – A critical review. Biotechnology Advances, 36(4), 1328–1340. https://doi.org/10.1016/j.biotechadv.2018.04.011

Bohonak, D. M., Mehta, U., Weiss, E. R., & Voyta, G. (2020). Adapting virus filtration to enable intensified and continuous monoclonal antibody processing. Biotechnology Progress, 37(2). https://doi.org/10.1002/btpr.3088

Bolton, G. R., & Mehta, K. K. (2016). The role of more than 40 years of improvement in protein A chromatography in the growth of the therapeutic antibody industry. Biotechnology Progress, 32(5), 1193–1202. https://doi.org/10.1002/btpr.2324

Buchsteiner, M., Quek, L., Gray, P., & Nielsen, L. K. (2018). Improving culture performance and antibody production in CHO cell culture processes by reducing the Warburg effect. Biotechnology and Bioengineering, 115(9), 2315–2327. https://doi.org/10.1002/bit.26724
Bulnes-Abundis, D., Carrillo-Cocom, L. M., Aráiz-Hernández, D., García-Ulloa, A., Granados-Pastor, M., Sánchez-Arreola, P. B., Murugappan, G., & Alvarez, M. M. (2012). A simple eccentric stirred tank mini-bioreactor: Mixing characterization and mammalian cell culture experiments. Biotechnology and Bioengineering, 110(4), 1106–1118. https://doi.org/10.1002/bit.24780
Clavaud, M., Roggo, Y., Von Daeniken, R., Liebler, A., & Schwabe, J.-O. (2013). Chemometrics and in-line near infrared spectroscopic monitoring of a biopharmaceutical Chinese hamster ovary cell culture: Prediction of multiple cultivation variables. Talanta, 111, 28–38. https://doi.org/10.1016/j.talanta.2013.03.044
Dangi, A. K., Sinha, R., Dwivedi, S., Gupta, S. K., & Shukla, P. (2018). Cell line techniques and gene editing tools for antibody production: A review. Frontiers in Pharmacology, 9. https://doi.org/10.3389/fphar.2018.00630
Datta, P., Linhardt, R. J., & Sharfstein, S. T. (2013). An 'omics approach towards CHO cell engineering. Biotechnology and Bioengineering, 110(5), 1255–1271. https://doi.org/10.1002/bit.24841
David, L., Niklas, J., Budde, B., Lobedann, M., & Schembecker, G. (2019). Continuous viral filtration for the production of monoclonal antibodies. Chemical Engineering Research and Design, 152, 336–347. https://doi.org/10.1016/j.cherd.2019.09.040
Dhara, V. G., Naik, H. M., Majewska, N. I., & Betenbaugh, M. J. (2018). Recombinant antibody production in CHO and NS0 cells: Differences and similarities. BioDrugs, 32(6), 571–584. https://doi.org/10.1007/s40259-018-0319-9
Ding, Y., Kumar, H., & Marino, M. (2019). Antibody purification process development and manufacturing. BioPharm International, 32(12), 24–29. https://www.biopharminternational.com/view/antibody-purification-process-development-and-manufacturing
Erkal, E. B., Baş, D., Köprülü, M., Korkmaz, M., Demirhan, D., & Can, O. (2021). Downstream processes for monoclonal antibody production. Journal of Health Institutes of Turkey, 85–93. https://dergipark.org.tr/tr/download/article-file/1740997
Fernandez‐Cerezo, L., Wismer, M. K., Han, I., & Pollard, J. M. (2019). High throughput screening of ultrafiltration and diafiltration processing of monoclonal antibodies via the ambr® crossflow system. Biotechnology Progress. https://doi.org/10.1002/btpr.2929
Freund, N., & Croughan, M. (2018). A simple method to reduce both lactic acid and ammonium production in industrial animal cell culture. International Journal of Molecular Sciences, 19(2), 385. https://doi.org/10.3390/ijms19020385
Fouladiha, H., Marashi, S.-A., Torkashvand, F., Mahboudi, F., Lewis, N. E., & Vaziri, B. (2020). A metabolic network-based approach for developing feeding strategies for CHO cells to increase monoclonal antibody production. Bioprocess and Biosystems Engineering, 43(8), 1381–1389. https://doi.org/10.1007/s00449-020-02332-6
Guertin, S. H. (2016). A packed-bed bioreactor system for enhancing vero cell growth in a semi-continuous mode of operation. Worcester Polytechnic Institute. https://www.semanticscholar.org/paper/A-Packed-Bed-Bioreactor-System-for-Enhancing-Vero-a-Guertin/20bd55ab99a62ac2d339b8cbe915c2460120d9f7
Hacker, D. L., & Wurm, F. M. (2017). Recombinant DNA technology for production of protein therapeutics in cultured mammalian cells. Reference Module in Life Sciences. https://doi.org/10.1016/b978-0-12-809633-8.09079-8
Haryadi, R., Ho, S., Kok, Y. J., Pu, H. X., Zheng, L., Pereira, N. A., Li, B., Bi, X., Goh, L.-T., Yang, Y., & Song, Z. (2015). Optimization of heavy chain and light chain signal peptides for high level expression of therapeutic antibodies in CHO Cells. PLOS ONE, 10(2). https://doi.org/10.1371/journal.pone.0116878
Hatton, T. S. (2012). Productivity studies utilizing recombinant CHO cells In stirred-tank bioreactors: A comparative study between the pitch-blade and the packed-bed bioreactor systems. All Graduate Theses and Dissertations. 1267. https://digitalcommons.usu.edu/etd/1267
Ho, S. C. L., Tong, Y. W., & Yang, Y. (2013-a). Generation of monoclonal antibody-producing mammalian cell lines. Pharmaceutical Bioprocessing, 1(1), 71–87. https://doi.org/10.4155/pbp.13.8
Ho, S. C. L., Koh, E. Y. C., van Beers, M., Mueller, M., Wan, C., Teo, G., Song, Z., Tong, Y. W., Bardor, M., & Yang, Y. (2013-b). Control of IGG LC:HC ratio in stably transfected CHO cells and study of the impact on expression, aggregation, glycosylation and conformational stability. Journal of Biotechnology, 165(3-4), 157–166. https://doi.org/10.1016/j.jbiotec.2013.03.019
Ho, S. C. L., Nian, R., Woen, S., Chng, J., Zhang, P., & Yang, Y. (2016). Impact of hydrolysates on monoclonal antibody productivity, purification and quality in Chinese hamster ovary cells. Journal of Bioscience and Bioengineering, 122(4), 499–506. https://doi.org/10.1016/j.jbiosc.2016.03.003
Hung, J. J., Borwankar, A. U., Dear, B. J., Truskett, T. M., & Johnston, K. P. (2016). High concentration tangential flow ultrafiltration of stable monoclonal antibody solutions with low viscosities. Journal of Membrane Science, 508, 113–126. https://doi.org/10.1016/j.memsci.2016.02.031
Inniss, M. C., Bandara, K., Jusiak, B., Lu, T. K., Weiss, R., Wroblewska, L., & Zhang, L. (2017). A novel Bxb1 integrase RMCE system for high fidelity site-specific integration of MAB expression cassette in CHO Cells. Biotechnology and Bioengineering, 114(8), 1837–1846. https://doi.org/10.1002/bit.26268
Jabra, M. G., Lipinski, A. M., & Zydney, A. L. (2021). Single Pass Tangential Flow Filtration (SPTFF) of monoclonal antibodies: Experimental studies and theoretical analysis. Journal of Membrane Science, 637, 119606. https://doi.org/10.1016/j.memsci.2021.119606
Jungbauer, A. (2013). Continuous downstream processing of biopharmaceuticals. Trends in Biotechnology, 31(8), 479–492. https://doi.org/10.1016/j.tibtech.2013.05.011
Karst, D. J., Scibona, E., Serra, E., Bielser, J.-M., Souquet, J., Stettler, M., Broly, H., Soos, M., Morbidelli, M., & Villiger, T. K. (2017). Modulation and modeling of monoclonal antibody N-linked glycosylation in mammalian cell perfusion reactors. Biotechnology and Bioengineering, 114(9), 1978–1990. https://doi.org/10.1002/bit.26315
Khan, K. H. (2013). Gene expression in mammalian cells and its applications. Advanced Pharmaceutical Bulletin, 3(2), 257-263. http://dx.doi.org/10.5681/apb.2013.042
Kishishita, S., Katayama, S., Kodaira, K., Takagi, Y., Matsuda, H., Okamoto, H., Takuma, S., Hirashima, C., & Aoyagi, H. (2015). Optimization of chemically defined feed media for monoclonal antibody production in Chinese hamster ovary cells. Journal of Bioscience and Bioengineering, 120(1), 78–84. https://doi.org/10.1016/j.jbiosc.2014.11.022

Kosiol, P., Hansmann, B., Ulbricht, M., & Thom, V. (2017). Determination of pore size distributions of virus filtration membranes using gold nanoparticles and their correlation with virus retention. Journal of Membrane Science, 533, 289–301. https://doi.org/10.1016/j.memsci.2017.03.043
Kruse, T., Schmidt, A., Kampmann, M., & Strube, J. (2019). Integrated clarification and purification of monoclonal antibodies by membrane based separation of aqueous two-phase systems. Antibodies, 8(3), 40. https://doi.org/10.3390/antib8030040
Kunert, R., & Reinhart, D. (2016). Advances in recombinant antibody manufacturing. Applied Microbiology and Biotechnology, 100(8), 3451–3461. https://doi.org/10.1007/s00253-016-7388-9
Kuwae, S., Miyakawa, I., & Doi, T. (2018). Development of a chemically defined platform fed-batch culture media for monoclonal antibody-producing CHO cell lines with optimized choline content. Cytotechnology, 70(3), 939–948. https://doi.org/10.1007/s10616-017-0185-1

Langer, E. S., & Rader, R. A. (2014). Continuous bioprocessing and perfusion: Wider adoption coming as bioprocessing matures. BioProcessing Journal, 13(1), 43–49. https://doi.org/10.12665/j131.langer

Li, F., Vijayasankaran, N., Shen, A. (Y., Kiss, R., & Amanullah, A. (2010). Cell Culture Processes for monoclonal antibody production. MAbs, 2(5), 466–479. https://doi.org/10.4161/mabs.2.5.12720

Li, Y.-mei, Tian, Z.-wei, Xu, D.-hua, Wang, X.-yin, & Wang, T.-yun. (2018). Construction strategies for developing expression vectors for recombinant monoclonal antibody production in CHO cells. Molecular Biology Reports, 45(6), 2907–2912. https://doi.org/10.1007/s11033-018-4351-0

Liu, B., Spearman, M., Doering, J., Lattová, E., Perreault, H., & Butler, M. (2014). The availability of glucose to CHO cells affects the intracellular lipid-linked oligosaccharide distribution, site occupancy and the N-glycosylation profile of a monoclonal antibody. Journal of Biotechnology, 170, 17–27. https://doi.org/10.1016/j.jbiotec.2013.11.007

Liu, A. P., Yan, Y., Wang, S., & Li, N. (2022). Coupling anion exchange chromatography with native mass spectrometry for charge heterogeneity characterization of monoclonal antibodies. Analytical Chemistry, 94(16), 6355–6362. https://doi.org/10.1021/acs.analchem.2c00707

Lloyd, E. C., Gandhi, T. N., & Petty, L. A. (2021). Monoclonal antibodies for COVID-19. JAMA, 325(10), 1015. https://doi.org/10.1001/jama.2021.1225

Madadkar, P., Sadavarte, R., Butler, M., Durocher, Y., & Ghosh, R. (2017). Preparative separation of monoclonal antibody aggregates by cation-exchange laterally-fed membrane chromatography. Journal of Chromatography B, 1055–1056, 158–164. https://doi.org/10.1016/j.jchromb.2017.04.036

Marichal-Gallardo, P. A., & Álvarez, M. M. (2012). State-of-the-art in downstream processing of monoclonal antibodies: Process trends in design and validation. Biotechnology Progress, 28(4), 899–916. https://doi.org/10.1002/btpr.1567

Mehta, K. K., & Vedantham, G. (2018). Next-generation process design for monoclonal antibody purification. Biopharmaceutical Processing, 793–811. https://doi.org/10.1016/b978-0-08-100623-8.00039-6

Moussa, E. M., Panchal, J. P., Moorthy, B. S., Blum, J. S., Joubert, M. K., Narhi, L. O., & Topp, E. M. (2016). Immunogenicity of therapeutic protein aggregates. Journal of Pharmaceutical Sciences, 105(2), 417–430. https://doi.org/10.1016/j.xphs.2015.11.002

Moustafa, Y. M., & Morsi, R. E. (2013). Ion exchange chromatography - an overview. Column Chromatography. https://doi.org/10.5772/55652

Nadar, S., Shooter, G., Somasundaram, B., Shave, E., Baker, K., & Lua, L. H. (2020). Intensified downstream processing of monoclonal antibodies using membrane technology. Biotechnology Journal, 16(3), 2000309. https://doi.org/10.1002/biot.202000309

Nasseri, S. S., Ghaffari, N., Braasch, K., Jardon, M. A., Butler, M., Kennard, M., Gopaluni, B., & Piret, J. M. (2014). Increased Cho cell fed-batch monoclonal antibody production using the autophagy inhibitor 3-ma or gradually increasing osmolality. Biochemical Engineering Journal, 91, 37–45. https://doi.org/10.1016/j.bej.2014.06.027

Natarajan, V., & Zydney, A. L. (2013). Protein a chromatography at high titers. Biotechnology and Bioengineering, 110(9), 2445–2451. https://doi.org/10.1002/bit.24902

Noh, S. M., Shin, S., & Lee, G. M. (2018). Comprehensive characterization of glutamine synthetase-mediated selection for the establishment of recombinant CHO cells producing monoclonal antibodies. Scientific Reports, 8(1). https://doi.org/10.1038/s41598-018-23720-9

O’Mara, P., Farrell, A., Bones, J., & Twomey, K. (2018). Staying alive! sensors used for monitoring cell health in bioreactors. Talanta, 176, 130–139. https://doi.org/10.1016/j.talanta.2017.07.088

Orellana, C. A., Marcellin, E., Schulz, B. L., Nouwens, A. S., Gray, P. P., & Nielsen, L. K. (2015). High-antibody-producing Chinese hamster ovary cells up-regulate intracellular protein transport and glutathione synthesis. Journal of Proteome Research, 14(2), 609–618. https://doi.org/10.1021/pr501027c

Pattison, J. R., & Patou, G. (2014). Parvoviruses. Nih.gov; University of Texas Medical Branch at Galveston. https://www.ncbi.nlm.nih.gov/books/NBK7715/#:~:text=Parvoviruses%20are%20non%2Denveloped%2C%20icosahedral,There%20are%20two%20capsid%20proteins.

Paul, A. J., Schwab, K., & Hesse, F. (2014). Direct analysis of mAb aggregates in mammalian cell culture supernatant. BMC Biotechnology, 14(1). https://doi.org/10.1186/s12896-014-0099-3

Pieracci, J. P., Armando, J. W., Westoby, M., & Thommes, J. (2018). Industry review of cell separation and product harvesting methods. Biopharmaceutical Processing, 165–206. https://doi.org/10.1016/b978-0-08-100623-8.00009-8

Pinto, I. F., Aires-Barros, M. R., & Azevedo, A. M. (2015). Multimodal chromatography: debottlenecking the downstream processing of monoclonal antibodies. Pharmaceutical Bioprocessing, 3(3), 263-279. 10.4155/pbp.15.7
Pollock, J., Ho, S. V., & Farid, S. S. (2012). Fed-batch and perfusion culture processes: Economic, environmental, and operational feasibility under uncertainty. Biotechnology and Bioengineering, 110(1), 206–219. https://doi.org/10.1002/bit.24608

Potter, H., & Heller, R. (2018). Transfection by electroporation. Current Protocols in Molecular Biology, 121(1). https://doi.org/10.1002/cpmb.48

Ramos‐de‐la‐Peña, A. M., González‐Valdez, J., & Aguilar, O. (2019). Protein A chromatography: Challenges and progress in the purification of monoclonal antibodies. Journal of Separation Science, 42(9), 1816–1827. https://doi.org/10.1002/jssc.201800963

Rashid, K., Hatton, T., Barnett, S., & Benninghoff, A. (2012). Productivity studies utilizing recombinant CHO cells in stirred-tank bioreactors: A comparative study between pitched-blade and packed-bed bioreactor systems. BioProcessing Journal, 11(2), 29–36. https://doi.org/10.12665/j112.rashid.pro

Rayfield, W. J., Roush, D. J., Chmielowski, R. A., Tugcu, N., Barakat, S., & Cheung, J. K. (2015). Prediction of viral filtration performance of monoclonal antibodies based on biophysical properties of feed. Biotechnology Progress, 31(3), 765–774. https://doi.org/10.1002/btpr.2094

Reinhart, D., Damjanovic, L., Kaisermayer, C., & Kunert, R. (2015). Benchmarking of commercially available CHO cell culture media for antibody production. Applied Microbiology and Biotechnology, 99(11), 4645–4657. https://doi.org/10.1007/s00253-015-6514-4

Saraswat, M., Musante, L., Ravidá, A., Shortt, B., Byrne, B., & Holthofer, H. (2013). Preparative purification of recombinant proteins: Current status and future trends. BioMed Research International, 2013, 1–18. https://doi.org/10.1155/2013/312709

Shi, C., Vogg, S., Lin, D., Sponchioni, M., & Morbidelli, M. (2021). Analysis and optimal design of batch and two‐column continuous chromatographic frontal processes for monoclonal antibody purification. Biotechnology and Bioengineering, 118(9), 3420–3434. https://doi.org/10.1002/bit.27763

Shukla, A. A., Wolfe, L. S., Mostafa, S. S., & Norman, C. (2017). Evolving trends in MAB Production Processes. Bioengineering & Translational Medicine, 2(1), 58–69. https://doi.org/10.1002/btm2.10061

Spearman, M., Lodewyks, C., Richmond, M., & Butler, M. (2014). The bioactivity and fractionation of peptide hydrolysates in cultures of CHO cells. Biotechnology Progress, 30(3), 584–593. https://doi.org/10.1002/btpr.1930

Steinebach, F., Ulmer, N., Wolf, M., Decker, L., Schneider, V., Wälchli, R., Karst, D., Souquet, J., & Morbidelli, M. (2017). Design and operation of a continuous integrated monoclonal antibody production process. Biotechnology Progress, 33(5), 1303–1313. https://doi.org/10.1002/btpr.2522

Stine, J. M., Beardslee, L. A., Sathyam, R. M., Bentley, W. E., & Ghodssi, R. (2020). Electrochemical dissolved oxygen sensor-integrated platform for wireless in situ Bioprocess Monitoring. Sensors and Actuators B: Chemical, 320, 128381. https://doi.org/10.1016/j.snb.2020.128381

Templeton, N., Dean, J., Reddy, P., & Young, J. D. (2013). Peak antibody production is associated with increased oxidative metabolism in an industrially relevant fed-batch CHO cell culture. Biotechnology and Bioengineering, 110(7), 2013–2024. https://doi.org/10.1002/bit.24858

Tyagi, S., Sharma, P. K., Kumar, N., & Visht, S. (2011). Hybridoma technique in pharmaceutical science. International Journal of PharmTech Research, 3(1), 459–463. https://www.sphinxsai.com/Vol.3No.1/pharm_jan-mar11/pdf/JM11(PT=76)%20pp%20459-463.pdf

Voronina, E. V., Seregin, Y. A., Litvinova, N. A., Shvets, V. I., & Shukurov, R. R. (2016). Design of a stable cell line producing a recombinant monoclonal anti-tnfα antibody based on a CHO cell line. SpringerPlus, 5(1). https://doi.org/10.1186/s40064-016-3213-2

Wurm, F., & Wurm, M. (2017). Cloning of CHO cells, productivity and genetic stability—a discussion. Processes, 5(4), 20. https://doi.org/10.3390/pr5020020

Xenopoulos, A. (2015). A new, integrated, continuous purification process template for monoclonal antibodies: Process modeling and cost of goods studies. Journal of Biotechnology, 213, 42–53. https://doi.org/10.1016/j.jbiotec.2015.04.020

Yamada, T., Yamamoto, K., Ishihara, T., & Ohta, S. (2017). Purification of monoclonal antibodies entirely in flow-through mode. Journal of Chromatography B, 1061-1062, 110–116. https://doi.org/10.1016/j.jchromb.2017.07.002

Ye, M., Wilhelm, M., Gentschev, I., & Szalay, A. (2021). A modified limiting dilution method for monoclonal stable cell line selection using a real-time fluorescence imaging system: A practical workflow and advanced applications. Methods and Protocols, 4(1), 16. https://doi.org/10.3390/mps4010016

Yuk, I. H., Russell, S., Tang, Y., Hsu, W.-T., Mauger, J. B., Aulakh, R. P. S., Luo, J., Gawlitzek, M., & Joly, J. C. (2014). Effects of copper on CHO cells: Cellular requirements and product quality considerations. Biotechnology Progress, 31(1), 226–238. https://doi.org/10.1002/btpr.2004

Zagari, F., Jordan, M., Stettler, M., Broly, H., & Wurm, F. M. (2013). Lactate metabolism shift in CHO cell culture: the role of mitochondrial oxidative activity. New Biotechnology, 30(2), 238–245. https://doi.org/10.1016/j.nbt.2012.05.021

Zboray, K., Sommeregger, W., Bogner, E., Gili, A., Sterovsky, T., Fauland, K., Grabner, B., Stiedl, P., Moll, H. P., Bauer, A., Kunert, R., & Casanova, E. (2015). Heterologous protein production using euchromatin-containing expression vectors in mammalian cells. Nucleic Acids Research, 43(16). https://doi.org/10.1093/nar/gkv475

Zhang, Y., Stobbe, P., Silvander, C. O., & Chotteau, V. (2015). Very high cell density perfusion of CHO cells anchored in a non-woven matrix-based bioreactor. Journal of Biotechnology, 213(10). https://doi.org/10.1016/j.jbiotec.2015.07.006

Zhang, Y. (2017). High cell density perfusion process development for antibody producing chinese hamster ovary cells. Royal Institute of Technology. http://www.diva-portal.org/smash/get/diva2:1097269/FULLTEXT01.pdf

Zhao, L., Fu, H.-Y., Zhou, W., & Hu, W.-S. (2015). Advances in process monitoring tools for Cell Culture bioprocesses. Engineering in Life Sciences, 15(5), 459–468. https://doi.org/10.1002/elsc.201500006

Zhu, J., & Hatton, D. (2017). New mammalian expression systems. New Bioprocessing Strategies: Development and Manufacturing of Recombinant Antibodies and Proteins, 9–50. https://doi.org/10.1007/10_2016_55

Zhu, M. M., Mollet, M., Hubert, R. S., Kyung, Y. S., & Zhang, G. G. (2017). Industrial production of therapeutic proteins: Cell lines, cell culture, and purification. Handbook of Industrial Chemistry and Biotechnology, 1639–1669. https://doi.org/10.1007/978-3-319-52287-6_29

Zydney, A. L. (2015). Continuous downstream processing for high value biological products: A review. Biotechnology and Bioengineering, 113(3), 465–475. https://doi.org/10.1002/bit.25695
Published
2023-03-24
How to Cite
Josefano, R., A, A., Dungus, C., Hamid, J., & Katherine, K. (2023). Bioprocessing of mAb (Monoclonal Antibodies) using Chinese Hamster Ovary (CHO) Cells: A Review. Indonesian Journal of Life Sciences, 5(01), 58-77. https://doi.org/https://doi.org/10.54250/ijls.v5i01.162
Section
Bio-product and Services for Sustainable Society