Advertisement

Effects of lithium on the secretory production of recombinant antibody from insect cells

  • Yuki Ohmuro-Matsuyama
  • Tomohisa Katsuda
  • Hideki YamajiEmail author
Article

Abstract

Monoclonal antibodies and antibody fragments are widely used in therapeutics and diagnoses. While mammalian cells serve as the host cells for antibody production, insect cells can produce large quantities of secretory antibodies in serum-free suspension cultures. The effects of lithium on the processes of autophagy and apoptosis in mammalian cells are well chronicled. In the present study, stably transformed insect cells, which produce an engineered antibody molecule, were cultured with lithium chloride in a serum-free medium. Treatment with lithium chloride induced autophagy and apoptosis in recombinant insect cells and led to increases in the yields of secreted antibodies.

Keywords

Insect cell culture Recombinant protein production Lithium chloride High Five cells Antibody 

Notes

Acknowledgements

This research was partially supported by the developing key technologies for discovering and manufacturing pharmaceuticals used for next-generation treatments and diagnoses both from the Ministry of Economy, Trade and Industry, Japan (METI) and from the Japan Agency for Medical Research and Development (AMED).

Supplementary material

11626_2018_303_MOESM1_ESM.pptx (1.5 mb)
ESM 1 (PPTX 1485 kb)

References

  1. Adler JT, Hottinger DG, Kunnimalaiyaan M, Chen H (2010) Inhibition of growth in medullary thyroid cancer cells with histone deacetylase inhibitors and lithium chloride. J Surg Res 159:640–644CrossRefGoogle Scholar
  2. Dell’Osso L, Grande CD, Gesi C, Carmassi C, Musetti L (2016) A new look at an old drug: neuroprotective effects and therapeutic potentials of lithium salt. Neuropsychiatr Dis Treat 12:1687–1703CrossRefGoogle Scholar
  3. Forlenza OV, De-Paula VJ, Diniz BS (2014) Neuroprotective effects of lithium: implications for the treatment of Alzheimer’s disease and related neurodegenerative disorders. ACS Chem Neurosci 5:443–450CrossRefGoogle Scholar
  4. Furuta T, Ogawa T, Yamaji H (2012) Production of antibody fragments using the baculovirus-insect cell system. Methods Mol Biol 907:371–387CrossRefGoogle Scholar
  5. Katsuda T, Sonoda H, Kumada Y, Yamaji H (2012) Production of antibody fragments in Escherichia coli. Methods Mol Biol 907:305–324CrossRefGoogle Scholar
  6. Kim JY, Kim YG, Lee GM (2012) CHO cells in biotechnology for production of recombinant proteins: current state and further potential. Appl Microbiol Biotechnol 93:917–930CrossRefGoogle Scholar
  7. Kunnimalaiyaan M, Vaccaro AM, Ndiaye MA, Chen H (2007) Inactivation of glycogen synthase kinase-3β, a downstream target of the raf-1 pathway, is associated with growth suppression in medullary thyroid cancer cells. Mol Cancer Ther 6:1151–1158CrossRefGoogle Scholar
  8. Lee JS, Lee GM (2012) Rapamycin treatment inhibits CHO cell death in a serum-free suspension culture by autophagy induction. Biotechnol Bioeng 109:3093–3102CrossRefGoogle Scholar
  9. Li L, Song H, Zhong L, Yang R, Yang XQ, Jiang KL, Liu BZ (2015) Lithium chloride promotes apoptosis in human leukemia NB4 cells by inhibiting glycogen synthase kinase-3 beta. Int J Med Sci 12:805–810CrossRefGoogle Scholar
  10. Menzel C, Schirrmann T, Konthur Z, Jostock T, Dubel S (2008) Human antibody RNase fusion protein targeting CD30+ lymphomas. Blood 111:3830–3837CrossRefGoogle Scholar
  11. Mohan C, Kim YG, Koo J, Lee GM (2008) Assessment of cell engineering strategies for improved therapeutic protein production in CHO cells. Biotechnol J 3:624–630CrossRefGoogle Scholar
  12. Motoi Y, Shimada K, Ishiguro K, Hattori N (2014) Lithium and autophagy. ACS Chem Neurosci 5:434–442CrossRefGoogle Scholar
  13. Ohmuro-Matsuyama Y, Mori K, Hamada H, Ueda H, Yamaji H (2017) Electrostatic engineering of the interface between heavy and light chains promotes antibody Fab fragment production. Cytotechnology 69:469–475CrossRefGoogle Scholar
  14. Omasa T, Onitsuka M, Kim WD (2010) Cell engineering and cultivation of Chinese hamster ovary (CHO) cells. Curr Pharm Biotechnol 11:233–240CrossRefGoogle Scholar
  15. Palmberger D, Rendic D, Tauber P, Krammer F, Wilson IB, Grabherr R (2011) Insect cells for antibody production: evaluation of an efficient alternative. J Biotechnol 153:160–166CrossRefGoogle Scholar
  16. Peng Z, Ji Z, Mei F, Lu M, Ou Y, Cheng X (2013) Lithium inhibits tumorigenic potential of PDA cells through targeting hedgehog-GLI signaling pathway. PLoS One 8:e61457CrossRefGoogle Scholar
  17. Pengo N, Scolari M, Oliva L, Milan E, Mainoldi F, Raimondi A, Fagioli C, Merlini A, Mariani E, Pasqualetto E, Orfanelli U, Ponzoni M, Sitia R, Casola S, Cenci S (2013) Plasma cells require autophagy for sustainable immunoglobulin production. Nat Immunol 14:298–305CrossRefGoogle Scholar
  18. Puttikhunt C, Keelapang P, Khemnu N, Sittisombut N, Kasinrerk W, Malasit P (2008) Novel anti-dengue monoclonal antibody recognizing conformational structure of the prM-E heterodimeric complex of dengue virus. J Med Virol 80:125–133CrossRefGoogle Scholar
  19. Sarkar S, Rubinsztein DC (2008) Huntington’s disease: degradation of mutant huntingtin by autophagy. FEBS J 275:4263–4270CrossRefGoogle Scholar
  20. Schlapschy M, Skerra A (2011) Periplasmic chaperones used to enhance functional secretion of proteins in E. coli. Methods Mol Biol 705:211–224CrossRefGoogle Scholar
  21. Schneider CA, Rasband WS, Eliceiri KW (2012) NIH Image to ImageJ: 25 years of image analysis. Nat Methods 9:671–675CrossRefGoogle Scholar
  22. Sonoda H, Kumada Y, Katsuda T, Yamaji H (2012) Production of single-chain Fv-Fc fusion protein in stably transformed insect cells. Biochem Eng J 67:77–82CrossRefGoogle Scholar
  23. Wang JS, Wang CL, Wen JF, Wang YJ, Hu YB, Ren HZ (2008) Lithium inhibits proliferation of human esophageal cancer cell line Eca-109 by inducing a G2/M cell cycle arrest. World J Gastroenterol 14:3982–3989CrossRefGoogle Scholar
  24. Yamaji H, Manabe T, Watakabe K, Muraoka M, Fujii I, Fukuda H (2008) Production of functional antibody Fab fragment by recombinant insect cells. Biochem Eng J 41:203–209CrossRefGoogle Scholar
  25. Yin Y, Kizer NT, Thaker PH, Chiappinelli KB, Trinkaus KM, Goodfellow PJ, Ma L (2013) Glycogen synthase kinase 3beta inhibition as a therapeutic approach in the treatment of endometrial cancer. Int J Mol Sci 14:16617–16637CrossRefGoogle Scholar
  26. Zeng Z, Wang H, Shang F, Zhou L, Little PJ, Quirion R, Zheng W (2016) Lithium ions attenuate serum-deprivation-induced apoptosis in PC12 cells through regulation of the Akt/FoxO1 signaling pathways. Psychopharmacology 233:785–794CrossRefGoogle Scholar

Copyright information

© The Society for In Vitro Biology 2018

Authors and Affiliations

  1. 1.Department of Chemical Science and Engineering, Graduate School of EngineeringKobe UniversityKobeJapan
  2. 2.Laboratory for Chemistry and Life Science, Institute for Innovative ResearchTokyo Institute of TechnologyYokohamaJapan
  3. 3.Manufacturing Technology Association of Biologics (MAB)c/o Integrated Research Center of Kobe UniversityKobeJapan

Personalised recommendations