Abstract
Most of the clinical approved protein-based drugs or under clinical trials have a profound impact on the treatment of critical diseases. The mammalian eukaryotic cells culture approaches, particularly the CHO (Chinese Hamster Ovary) cells are mainly used in the biopharmaceutical industry for the mass-production of the therapeutic protein. Recent advances in CHO cell bioprocessing to yield recombinant proteins and monoclonal antibodies have enabled the expression of quality protein. The developments of cell lines are possible to enhance specific productivity. As a result, it holds an interesting area for academic as well as industrial researchers around the world. This review will focus on the recent progress of the mammalian CHO cells culture technology and the future scope of further development for the mass-production of protein therapeutics.
Keywords: Therapeutic protein, mammalian cells, CHO cells, protein expression, bio-processing, mass-production.
Graphical Abstract
[1]
Wurm FM. Production of recombinant protein therapeutics in cultivated mammalian cells. Nat Biotechnol 2004; 22(11): 1393-8.
[http://dx.doi.org/10.1038/nbt1026] [PMID: 15529164]
[http://dx.doi.org/10.1038/nbt1026] [PMID: 15529164]
[2]
Cacciatore JJ, Chasin LA, Leonard EF. Gene amplification and vector engineering to achieve rapid and high-level therapeutic protein production using the Dhfr-based CHO cell selection system. Biotechnol Adv 2010; 28(6): 673-81.
[http://dx.doi.org/10.1016/j.biotechadv.2010.04.003] [PMID: 20416368]
[http://dx.doi.org/10.1016/j.biotechadv.2010.04.003] [PMID: 20416368]
[3]
Pearson S. Producing protein therapeutics by mammalian cell culture. Bioprocess Int 2007; 5: 30-7.
[4]
Chu L, Robinson DK. Industrial choices for protein production by large-scale cell culture. Curr Opin Biotechnol 2001; 12(2): 180-7.
[http://dx.doi.org/10.1016/S0958-1669(00)00197-X] [PMID: 11287235]
[http://dx.doi.org/10.1016/S0958-1669(00)00197-X] [PMID: 11287235]
[5]
Kim JY, Kim YG, Lee GM. CHO cells in biotechnology for production of recombinant proteins: Current state and further potential. Appl Microbiol Biotechnol 2012; 93(3): 917-30.
[http://dx.doi.org/10.1007/s00253-011-3758-5] [PMID: 22159888]
[http://dx.doi.org/10.1007/s00253-011-3758-5] [PMID: 22159888]
[6]
Li F, Vijayasankaran N, Shen A, Kiss R, Amanullah A. 2010 pp. Cell culture processes for monoclonal antibody production. MAbs 2 466-477.
[http://dx.doi.org/10.4161/mabs.2.5.12720]
[http://dx.doi.org/10.4161/mabs.2.5.12720]
[7]
Kim SH, Lee GM. Development of serum-free medium supplemented with hydrolysates for the production of therapeutic antibodies in CHO cell cultures using design of experiments. Appl Microbiol Biotechnol 2009; 83(4): 639-48.
[http://dx.doi.org/10.1007/s00253-009-1903-1] [PMID: 19266194]
[http://dx.doi.org/10.1007/s00253-009-1903-1] [PMID: 19266194]
[8]
Brunner D, Frank J, Appl H, Schöffl H, Pfaller W, Gstraunthaler G. The serum-free media interactive online database. ALTEX-. Altern Anim Exp 2010; 27(1): 53-62.
[http://dx.doi.org/10.14573/altex.2010.1.53]
[http://dx.doi.org/10.14573/altex.2010.1.53]
[9]
Kim SJ, Kim NS, Ryu CJ, Hong HJ, Lee GM. Characterization of chimeric antibody producing CHO cells in the course of dihydrofolate reductase-mediated gene amplification and their stability in the absence of selective pressure. Biotechnol Bioeng 1998; 58(1): 73-84.
[http://dx.doi.org/10.1002/(SICI)1097-0290(19980405)58:1<73::AID-BIT8>3.0.CO;2-R] [PMID: 10099263]
[http://dx.doi.org/10.1002/(SICI)1097-0290(19980405)58:1<73::AID-BIT8>3.0.CO;2-R] [PMID: 10099263]
[10]
Bandaranayake AD, Almo SC. Recent advances in mammalian protein production. FEBS Lett 2014; 588(2): 253-60.
[http://dx.doi.org/10.1016/j.febslet.2013.11.035] [PMID: 24316512]
[http://dx.doi.org/10.1016/j.febslet.2013.11.035] [PMID: 24316512]
[11]
Chadd HE, Chamow SM. Therapeutic antibody expression technology. Curr Opin Biotechnol 2001; 12(2): 188-94.
[http://dx.doi.org/10.1016/S0958-1669(00)00198-1] [PMID: 11287236]
[http://dx.doi.org/10.1016/S0958-1669(00)00198-1] [PMID: 11287236]
[12]
Baik JY, Lee KH. A framework to quantify karyotype variation associated with CHO cell line instability at a single-cell level. Biotechnol Bioeng 2017; 114(5): 1045-53.
[http://dx.doi.org/10.1002/bit.26231] [PMID: 27922175]
[http://dx.doi.org/10.1002/bit.26231] [PMID: 27922175]
[13]
Nunberg JH, Kaufman RJ, Schimke RT, Urlaub G, Chasin LA. Amplified dihydrofolate reductase genes are localized to a homogeneously staining region of a single chromosome in a methotrexate-resistant Chinese hamster ovary cell line. Proc Natl Acad Sci USA 1978; 75(11): 5553-6.
[http://dx.doi.org/10.1073/pnas.75.11.5553] [PMID: 281704]
[http://dx.doi.org/10.1073/pnas.75.11.5553] [PMID: 281704]
[14]
Bebbington CR, Renner G, Thomson S, King D, Abrams D, Yarranton GT. High-level expression of a recombinant antibody from myeloma cells using a glutamine synthetase gene as an amplifiable selectable marker. Biotechnology (N Y) 1992; 10(2): 169-75.
[PMID: 1369477]
[PMID: 1369477]
[15]
Peroni CN, Soares CR, Gimbo E, Morganti L, Ribela MT, Bartolini P. High-level expression of human thyroid-stimulating hormone in Chinese hamster ovary cells by co-transfection of dicistronic expression vectors followed by a dual-marker amplification strategy. Biotechnol Appl Biochem 2002; 35(1): 19-26.
[http://dx.doi.org/10.1042/BA20010061] [PMID: 11834126]
[http://dx.doi.org/10.1042/BA20010061] [PMID: 11834126]
[16]
Xiong KH, Liang QC, Xiong H, et al. Expression of chimeric antibody in mammalian cells using dicistronic expression vector. Biotechnol Lett 2005; 27(21): 1713-7.
[http://dx.doi.org/10.1007/s10529-005-2736-3] [PMID: 16247680]
[http://dx.doi.org/10.1007/s10529-005-2736-3] [PMID: 16247680]
[17]
Ng SK, Wang DI, Yap MG. Application of destabilizing sequences on selection marker for improved recombinant protein productivity in CHO-DG44. Metab Eng 2007; 9(3): 304-16.
[http://dx.doi.org/10.1016/j.ymben.2007.01.001] [PMID: 17368064]
[http://dx.doi.org/10.1016/j.ymben.2007.01.001] [PMID: 17368064]
[18]
Mohan C, Kim YG, Koo J, Lee GM. Assessment of cell engineering strategies for improved therapeutic protein production in CHO cells. Biotechnol J 2008; 3(5): 624-30.
[http://dx.doi.org/10.1002/biot.200700249] [PMID: 18293320]
[http://dx.doi.org/10.1002/biot.200700249] [PMID: 18293320]
[19]
Arden N, Betenbaugh MJ. Life and death in mammalian cell culture: strategies for apoptosis inhibition. Trends Biotechnol 2004; 22(4): 174-80.
[http://dx.doi.org/10.1016/j.tibtech.2004.02.004] [PMID: 15038922]
[http://dx.doi.org/10.1016/j.tibtech.2004.02.004] [PMID: 15038922]
[20]
Chiang GG, Sisk WP. Bcl-x(L) mediates increased production of humanized monoclonal antibodies in Chinese hamster ovary cells. Biotechnol Bioeng 2005; 91(7): 779-92.
[http://dx.doi.org/10.1002/bit.20551] [PMID: 15986489]
[http://dx.doi.org/10.1002/bit.20551] [PMID: 15986489]
[21]
Yang M, Butler M. Effects of ammonia on CHO cell growth, erythropoietin production, and glycosylation. Biotechnol Bioeng 2000; 68(4): 370-80.
[http://dx.doi.org/10.1002/(SICI)1097-0290(20000520)68:4<370::AID-BIT2>3.0.CO;2-K] [PMID: 10745205]
[http://dx.doi.org/10.1002/(SICI)1097-0290(20000520)68:4<370::AID-BIT2>3.0.CO;2-K] [PMID: 10745205]
[22]
Kumar N, Gammell P, Meleady P, Henry M, Clynes M. Differential protein expression following low temperature culture of suspension CHO-K1 cells. BMC Biotechnol 2008; 8(1): 42.
[http://dx.doi.org/10.1186/1472-6750-8-42] [PMID: 18430238]
[http://dx.doi.org/10.1186/1472-6750-8-42] [PMID: 18430238]
[23]
Feng Y, Dimitrov DS. Scaling-up and production of therapeutic antibodies for preclinical studies InTherapeutic Antibodies. Humana Press 2009; pp. 499-508.
[24]
Domann R, Martinez J. Alternative to cloning cylinders for isolation of adherent cell clones. Biotechniques 1995; 18(4): 594-5.
[PMID: 7598885]
[PMID: 7598885]
[25]
Borth N, Zeyda M, Kunert R, Katinger H. Efficient selection of high-producing subclones during gene amplification of recombinant Chinese hamster ovary cells by flow cytometry and cell sorting. Biotechnol Bioeng 2000-2001; 71(4): 266-73.
[http://dx.doi.org/10.1002/1097-0290(2000)71:4<266::AIDBIT1016>3.0.CO;2-2] [PMID: 11291036]
[http://dx.doi.org/10.1002/1097-0290(2000)71:4<266::AIDBIT1016>3.0.CO;2-2] [PMID: 11291036]
[26]
Pichler J, Hesse F, Wieser M, et al. A study on the temperature dependency and time course of the cold capture antibody secretion assay. J Biotechnol 2009; 141(1-2): 80-3.
[http://dx.doi.org/10.1016/j.jbiotec.2009.03.001] [PMID: 19428734]
[http://dx.doi.org/10.1016/j.jbiotec.2009.03.001] [PMID: 19428734]
[27]
Hanania EG, Fieck A, Stevens J, Bodzin LJ, Palsson BØ, Koller MR. Automated in situ measurement of cell-specific antibody secretion and laser-mediated purification for rapid cloning of highly-secreting producers. Biotechnol Bioeng 2005; 91(7): 872-6.
[http://dx.doi.org/10.1002/bit.20559] [PMID: 15937942]
[http://dx.doi.org/10.1002/bit.20559] [PMID: 15937942]
[28]
Xing Z, Kenty BM, Li ZJ, Lee SS. Scale-up analysis for a CHO cell culture process in large-scale bioreactors. Biotechnol Bioeng 2009; 103(4): 733-46.
[http://dx.doi.org/10.1002/bit.22287] [PMID: 19280669]
[http://dx.doi.org/10.1002/bit.22287] [PMID: 19280669]
[29]
Shukla AA, Thömmes J. Recent advances in large-scale production of monoclonal antibodies and related proteins. Trends Biotechnol 2010; 28(5): 253-61.
[http://dx.doi.org/10.1016/j.tibtech.2010.02.001] [PMID: 20304511]
[http://dx.doi.org/10.1016/j.tibtech.2010.02.001] [PMID: 20304511]
[30]
Lai T, Yang Y, Ng SK. Advances in Mammalian cell line development technologies for recombinant protein production. Pharmaceuticals (Basel) 2013; 6(5): 579-603.
[http://dx.doi.org/10.3390/ph6050579] [PMID: 24276168]
[http://dx.doi.org/10.3390/ph6050579] [PMID: 24276168]
[31]
Kim HW, Estep TN. Practical considerations in the development of hemoglobin-based oxygen therapeutics. Curr Drug Discov Technol 2012; 9(3): 212-23.
[http://dx.doi.org/10.2174/157016312802650779] [PMID: 21726184]
[http://dx.doi.org/10.2174/157016312802650779] [PMID: 21726184]
[32]
Lee MK. Clinical usefulness of liposomal formulations in cancer therapy: lessons from the experiences of doxorubicin. J Pharm Investig 2019; 49(2): 203-14.
[http://dx.doi.org/10.1007/s40005-018-0398-0]
[http://dx.doi.org/10.1007/s40005-018-0398-0]
Article Metrics
154
1