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| Recent Advances in Cell Engineering for Monoclonal Antibody Production |
| HUI Kai-yuan1, GAO Xiang-dong1, XU Chen2 |
1. Life Science and Technology Department, China Pharmaceutical University, Nanjing 210009, China;
2. Beijing Tri-Prime Genetic Engineering Co., Ltd. Beijing 102600, China |
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Abstract Monoclonal antibody (mAb) with increasing importance to modern medicine is currently one of the major biopharmaceutical products in development. Mammalian cells are the preferred host for the manufacture of mAb, but production costs are still high with a low productivity. A range of rational engineering strategies have been pursued in order to increase volumetric yield of production from mammalian cells, such as delaying apoptosis, manipulating the cell cycle, and improving metabolism and protein processing. Many engineering strategies developed to date are reviewed and the possible areas of research in the future are discussed.
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Received: 30 August 2011
Published: 25 February 2012
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[1] Rita C A, Elisa R M, Henriques M, et al. Guidelines to cell engineering for monoclonal antibody production. European Journal of Pharmaceutics and Biopharmaceutics, 2010, 74(2):127-138.
[2] Rodrigues M E, Costa A R, Henriques M, et al. Technological progresses in monoclonal antibody production systems. Biotechnology Progress, 2010, 26(2):332-351.
[3] Hansel T T, Kropshofer H, Singer T, et al. The safety and side effects of monoclonal antibodies. Nature Reviews: Drug Discovery, 2010, 9(4):325-338.
[4] Mohan C, Kim Y G, Koo J, et al. Assessment of cell engineering strategies for improved therapeutic protein production in CHO cells. Biotechnology Journal, 2008, 3(5):624-630.
[5] Majors B S, Betenbaugh M J, Pederson N E, et al. Mcl-1 overexpression leads to higher viabilities and increased production of humanized monoclonal antibody in Chinese hamster ovary cells. Biotechnology Progress, 2009,25(4):1161-1168.
[6] Kim N S, Lee G M. Overexpression of bcl-2 inhibits sodium butyrate-induced apoptosis in Chinese hamster ovary cells resulting in enhanced humanized antibody production. Biotechnology and Bioengineering, 2000. 71(3): p. 184-193.
[7] Majors B S, Betenbaugh M J, Pederson N E, et al. Mcl-1 overexpression leads to higher viabilities and increased production of humanized monoclonal antibody in Chinese hamster ovary cells. Biotechnology Progress, 2009, 25(4):1161-1168.
[8] Koo T Y, Park J H, Park H H, et al. Beneficial effect of 30Kc6 gene expression on production of recombinant interferon- in serum-free suspension culture of CHO cells. Process Biochemistry, 2009, 44(2):146-153.
[9] Cost G J, Freyvert Y, Vafiadis A, et al. BAK and BAX deletion using zinc-finger nucleases yields apoptosis resistant CHO cells. Biotechnology and Bioengineering, 2010, 105(2):330-340.
[10] Arden N, Majors B S, Ahn S, et al. Inhibiting the apoptosis pathway using MDM2 in mammalian cell cultures. Biotechnology and Bioengineering, 2007, 97(3):601-614.
[11] Sung Y H, Lee J S, Park S H, et al. Influence of co-down-regulation of caspase-3 and caspase-7 by siRNAs on sodium butyrate-induced apoptotic cell death of Chinese hamster ovary cells producing thrombopoietin. Metabolic Engineering, 2007, 9(5-6):452-464.
[12] Yiping L,Niki S C,Yin Y L, et al. Engineering mammalian cells in bioprocessing-current achievements and future perspectives. Biotechnology and Applied Biochemistry, 2010, 55(4):175-189.
[13] Kim S H, Lee G M. Functional expression of human pyruvate carboxylase for reduced lactic acid formation of Chinese hamster ovary cells (DG44). Applied Microbiology and Biotechnology, 2007, 76(3):659-665.
[14] Kim S H, Lee G M. Down-regulation of lactate dehydrogenase-A by siRNAs for reduced lactic acid formation of Chinese hamster ovary cells producing thrombopoietin. Applied Microbiology and Biotechnology, 2007, 74(1):152-159.
[15] Nolan R P, Lee K. Dynamic model of CHO cell metabolism. Metabolic Engineering, 2010,13(1):108-124.
[16] Kim H Y, Tsai S, Wear D J, et al. Production and characterization of chimeric monoclonal antibodies against Burkholderia pseudomallei and B. mallei using the DHFR expression system. PloS One, 2011,6(5):e19867.
[17] Tanaka T, Rabbitts T H. Protocol for the selection of single-domain antibody fragments by third generation intracellular antibody capture. Nature Protocols, 2009,5(1):67-92.
[18] Ku S C, Yao M G, Chao S H. Effects of overexpression of X-box binding protein 1 on recombinant protein production in Chinese hamster ovary and NS0 myeloma cells. Biotechnology and Bioengineering, 2008,99(1):155-164.
[19] Conradie R, Bruggeman F J, Ciliberto A, et al. Restriction point control of the mammalian cell cycle via the cyclin E/Cdk2: p27 complex. FEBS Journal, 2010, 277(2):357-367.
[20] Werner N S, Weber W, Fussenegger M, et al. A gas-inducible expression system in HEK. EBNA cells applied to controlled proliferation studies by expression of p27Kip1. Biotechnology and Bioengineering, 2007, 96(6):1155-1166.
[21] Ku S C Y, Yap M G S, Chao S H. Effects of overexpression of X-box binding protein 1 on recombinant protein production in Chinese hamster ovary and NS0 myeloma cells. Biotechnology and Bioengineering, 2008, 99(1):155-164.
[22] Becker E, Florin L, Pfizenmaier K, et al. An XBP-1 dependent bottle-neck in production of IgG subtype antibodies in chemically defined serum-free Chinese hamster ovary (CHO) fed-batch processes. Journal of Biotechnology, 2008, 135(2):217-223.
[23] Mohan C, Park S H, Chung J Y, et al. Effect of doxycycline regulated protein disulfide isomerase expression on the specific productivity of recombinant CHO cells: Thrombopoietin and antibody. Biotechnology and Bioengineering, 2007, 98(3):611-615.
[24] Jin F, Kretschmer P J, Harkins R N, et al. Enhanced protein production using HBV X protein (HBx), and synergy when used in combination with XBP1s in BHK21 cells. Biotechnology and Bioengineering, 2010, 105(2):341-349.
[25] Peng R W, Fussenegger M. Molecular engineering of exocytic vesicle traffic enhances the productivity of Chinese hamster ovary cells. Biotechnology and Bioengineering, 2009, 102(4):1170-1181.
[26] Peng R W, Guetg C, Tigges M, et al. The vesicle-trafficking protein munc18b increases the secretory capacity of mammalian cells. Metabolic Engineering, 2010, 12(1):18-25.
[27] Jefferis R. Glycosylation as a strategy to improve antibody-based therapeutics. Nature Reviews Drug Discovery, 2009, 8(3):226-234.
[28] Gammell P, Barron N, Kumar N, et al. Initial identification of low temperature and culture stage induction of miRNA expression in suspension CHO-K1 cells. Journal of Biotechnology, 2007, 130(3):213-218.
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