Journal of Plant Biotechnology

The Korean Society of Plant Biotechnology (한국식물생명공학회)
권호 표지
DOI QR코드

DOI QR Code

Impacts of glycans attached to therapeutic glycoproteins

의약용 당단백질에 부가된 당사슬의 중요성

  • Kim, Seong-Hun (Integrative Omics Research Center, Korea Research Institute of Bioscience & Biotechnology) ;
  • Kwon, Oh-Suk (Integrative Omics Research Center, Korea Research Institute of Bioscience & Biotechnology) ;
  • Oh, Doo-Byoung (Integrative Omics Research Center, Korea Research Institute of Bioscience & Biotechnology)
  • 김성훈 (한국생명공학연구원 오믹스융합연구센터) ;
  • 권오석 (한국생명공학연구원 오믹스융합연구센터) ;
  • 오두병 (한국생명공학연구원 오믹스융합연구센터)
  • Received : 2010.08.09
  • Accepted : 2010.08.20
  • Published : 2010.09.30
Download PDF
⟨ Previous Next ⟩

Abstract

High value-added therapeutic proteins have been leading the biologics industry and occupied major portion of the market. More than 60% of the currently available protein therapeutics are glycoproteins attached with glycans which play crucial roles for the protein folding, therapeutic efficacy, in vivo half-life and immunogenecity. This review introduces the process of glycosylation and the impacts of glycans in the aspects of therapeutics. The important glycan structures in therapeutic performances were also summarized focusing on three representative categories of glycoproteins, cytokines, therapeutic antibody and enzyme. Currently, mammalian expression systems such as Chinese hamster ovary cells are preferred for the production of therapeutic glycoproteins due to their ability to synthesize glycans having similar structures with human type glycans. However, recent advances of plant glycoengineering to overcome the limitation originating from different glycan structures will soon allow to develop more efficient and economic plant-based production systems for therapeutic glycoproteins.

Keywords

References

  1. Aebi M, Bernasconi R, Clerc S, Molinari M (2010) N-glycan structures: recognition and processing in the ER. Trends Biochem Sci 35:74-82 https://doi.org/10.1016/j.tibs.2009.10.001
  2. Anthony RM, Nimmerjahn F, Ashline DJ, Reinhold VN, Paulson JC, Ravetch JV (2008) Recapitulation of IVIG antiinflammatory activity with a recombinant IgG Fc. Science 320:373-376 https://doi.org/10.1126/science.1154315
  3. Ashwell G, Kawasaki T (1978) A protein from mammalian liver that specifically binds galactose-terminated glycoproteins. Methods Enzymol 50:287-288. https://doi.org/10.1016/0076-6879(78)50029-3
  4. Boyd PN, Lines AC, Patel AK (1995) The effect of the removal of sialic acid, galactose and total carbohydrate on the functional activity of Campath-1H. Mol Immunol 32:1311-1318 https://doi.org/10.1016/0161-5890(95)00118-2
  5. Chavan M, Yan A, Lennarz WJ (2005) Subunits of the translocon interact with components of the oligosaccharyltransferase complex. J Biol Chem 280:22917-22924 https://doi.org/10.1074/jbc.M502858200
  6. Chou HH, Hayakawa T, Diaz S, Krings M, Indriati E, Leakey M, Paabo S, Satta Y, Takahata N, Varki A (2002) Inactivation of CMP-N-acetylneuraminic acid hydroxylase occurred prior to brain expansion during human evolution. Proc Natl Acad Sci USA 99:11736-11741 https://doi.org/10.1073/pnas.182257399
  7. Chung CH, Mirakhur B, Chan E, Le QT, Berlin J, Morse M, Murphy BA, Satinover SM, Hosen J, Mauro D, Slebos RJ, Zhou Q, Gold D, Hatley T, Hicklin DJ, Platts-Mills TA (2008) Cetuximab-induced anaphylaxis and IgE specific for galactose-alpha-1,3-galactose. N Engl J Med 358:1109-1117 https://doi.org/10.1056/NEJMoa074943
  8. Cox KM, Sterling JD, Regan JT, Gasdaska JR, Frantz KK, Peele CG, Black A, Passmore D, Moldovan-Loomis C, Srinivasan M, Cuison S, Cardarelli PM, Dickey LF (2006) Glycan optimization of a human monoclonal antibody in the aquatic plant Lemna minor. Nat Biotechnol 24:1591-1597 https://doi.org/10.1038/nbt1260
  9. Elliott S, Egrie J, Browne J, Lorenzini T, Busse L, Rogers N, Ponting I (2004) Control of rHuEPO biological activity: the role of carbohydrate. Exp Hematol 32:1146-1155 https://doi.org/10.1016/j.exphem.2004.08.004
  10. Erbayraktar S, Grasso G, Sfacteria A, Xie QW, Coleman T, Kreilgaard M, Torup L, Sager T, Erbayraktar Z, Gokmen N, Yilmaz O, Ghezzi P, Villa P, Fratelli M, Casagrande S, Leist M, Helboe L, Gerwein J, Christensen S, Geist MA, Pedersen LO, Cerami-Hand C, Wuerth JP, Cerami A, Brines M (2003) Asialoerythropoietin is a nonerythropoietic cytokine with broad neuroprotective activity in vivo. Proc Natl Acad Sci USA 100:6741-6746 https://doi.org/10.1073/pnas.1031753100
  11. Ernst JF, Mermod JJ, Richman LH (1992) Site-specific O-glycosylation of human granulocyte/macrophage colonystimulating factor secreted by yeast and animal cells. Eur J Biochem/FEBS 203:663-667 https://doi.org/10.1111/j.1432-1033.1992.tb16596.x
  12. FDA (US Food and Drug Administration) website: http://www.fda.gov/downloads/Drugs/DevelopmentApprovalProcess/HowDrugsareDevelopedandApproved/ApprovalApplications/TherapeuticBiologicApplications/ucm113330.pdf
  13. Ferra C, Brunker P, Suter T, Moser S, Püntener U, Umana P (2006) Modulation of therapeutic antibody effector functions by glycosylation engineering. Biotechnol Bioeng 93:851-861 https://doi.org/10.1002/bit.20777
  14. Flesher AR Marzowski J, Wang WC, Raff HV (1995) Fluorophorelabeled carbohydrate analysis of immunoglobulin fusion proteins. Biotechnol Bioeng 46:399-407 https://doi.org/10.1002/bit.260460502
  15. Fujiyama K, Misaki R, Sakai Y, Omasa T, Seki T (2009) Change in glycosylation pattern with extension of endoplasmic reticulum retention signal sequence of mouse antibody produced by suspension-cultured tobacco BY2 cells. J Biosci Bioeng 107:165-172 https://doi.org/10.1016/j.jbiosc.2008.09.016
  16. Gomord V, Fitchette AC, Menu-Bouaouiche L, Saint-Jore-Dupas C, Plasson C, Michaud D, Faye L (2010) Plant-specific glycosylation patterns in the context of therapeutic protein production. Plant Biotechnol J 8:564-857 https://doi.org/10.1111/j.1467-7652.2009.00497.x
  17. Grewal PK, Uchiyama S, Ditto D, Varki N, Le DT, Nizet V, Marth JD (2008) The Ashwell receptor mitigates the lethal coagulopathy of sepsis. Nat Med 14:648-655 https://doi.org/10.1038/nm1760
  18. Helenius A, Aebi M (2004) Roles of N-linked glycans in the endoplasmic reticulum. Ann Rev Biochem 73:1019-1049 https://doi.org/10.1146/annurev.biochem.73.011303.073752
  19. Jin C, Altmann F, Strasser R, Mach L, Schahs M, Kunert R, Rademacher T, Glossl J, Steinkellner H (2008) A plantderived human monoclonal antibody induces an anticarbohydrate immune response in rabbits. Glycobiology 18: 235-241 https://doi.org/10.1093/glycob/cwm137
  20. Jones AJ, Papac DI, Chin EH, Keck R, Baughman SA, Lin YS, Kneer J, Battersby JE (2007) Selective clearance of glycoforms of a complex glycoprotein pharmaceutical caused by terminal N-acetylglucosamine is similar in humans and cynomolgus monkeys. Glycobiology 17:529-540 https://doi.org/10.1093/glycob/cwm017
  21. Julenius K, Molgaard A, Gupta R, Brunak S (2005) Prediction, conservation analysis and structural characterization of mammalian mucin-type O-glycosylation sites. Glycobiology 15:153-164 https://doi.org/10.1093/glycob/cwh151
  22. Kaneko Y, Nimmerjahn F & Ravethc JV (2006) Antiinflammatory activity of immunoglobulin G resulting from Fc sialylation. Science 313:670-673 https://doi.org/10.1126/science.1129594
  23. Kelleher DJ, Banerjee S, Cura AJ, Samuelson J, Gilmore R (2007) Dolichol-linked oligosaccharide selection by the oligosaccharyltransferase in protist and fungal organisms. J Cell Biol 177:29-37 https://doi.org/10.1083/jcb.200611079
  24. Kelleher DJ, Gilmore R (1994) The Saccharomyces cerevisiae oligosaccharyltransferase is a protein complex composed of Wbp1p, Swp1p, and four additional polypeptides. J Biol Chem 269:12908-12917
  25. Ko K, Ahn MH, Song M, Choo YK, Kim HS, Ko K, Joung H (2008) Glyco-engineering of biotherapeutic proteins in plants. Mol Cells 25:494-503
  26. Ko K, Tekoah Y, Rudd PM, Harvey DJ, Dwek RA, Spitsin S, Hanlon CA, Rupprecht C, Dietzschold B, Golovkin M, Koprowski H (2003) Function and glycosylation of plantderived antiviral monoclonal antibody. Proc Natl Acad Sci USA 100:8013-8018 https://doi.org/10.1073/pnas.0832472100
  27. Krapp S, Mimura Y, Jefferis R, Huber R, Sondermann P (2003) Structural analysis of human IgG-Fc glycoforms reveals a correlation between glycosylation and structural integrity. J Mol Biol 325:979-989 https://doi.org/10.1016/S0022-2836(02)01250-0
  28. Maynard Y, Baenziger JU (1981) Oligosaccharide specific endocytosis by isolated rat hepatic reticuloendothelial cells. J Biol Chem 256:8063-8068
  29. Nechansky A, Schuster M, Jost W, Siegl P, Wiederkum S, Gorr G, Kircheis R (2007) Compensation of endogeneous IgG mediated inhibition of antibody-dependent cellular cytotoxicity by glyco-engineering of the therapeutic antibodies. Mol Immunol 44:1815-1817 https://doi.org/10.1016/j.molimm.2006.08.013
  30. Nimmerjahn F, Ravetch J (2008) Fc receptors as regulators of immune responses. Nature Rev Immunol 8:34-47 https://doi.org/10.1038/nri2206
  31. Pattison RJ, Amtmann A (2009) N-glycan production in the endoplasmic reticulum of plants. Trends Plant Sci 14:92-99 https://doi.org/10.1016/j.tplants.2008.11.008
  32. Peipp M, Lammerts van Bueren JJ, Schneider-Merck T, Bleeker WW, Dechant M, Beyer T, Repp R, van Berkel PH, Vink T, van de Winkel JG, Parren PW, Valerius T (2008) Antibody fucosylation differentially impacts cytotoxicity mediated by NK and PMN effector cells. Blood 112:2390-2399 https://doi.org/10.1182/blood-2008-03-144600
  33. Potgieter TI, Cukan M, Drummond JE, Houston-Cummings NR, Jiang Y, Li F, Lynaugh H, Mallem M, McKelvey TW, Mitchell T, Nylen A, Rittenhour A, Stadheim TA, Zha D, d’Anjou M (2009) Production of monoclonal antibodies by glycoengineered Pichia pastoris. J Biotechnol 139:318-325 https://doi.org/10.1016/j.jbiotec.2008.12.015
  34. Rademacher TW (1993) Glycosylation as a factor affecting product consistency. Biologicals 21:103-104 https://doi.org/10.1006/biol.1993.1056
  35. Ruddock LW, Molinari M (2006) N-glycan processing in ER quality control. J Cell Sci 119:4373-4380 https://doi.org/10.1242/jcs.03225
  36. Saint-Jore-Dupas C, Faye L, Gomord V (2007) From planta to pharma with glycosylation in the toolbox. Trends Biotechnol 25:317-323 https://doi.org/10.1016/j.tibtech.2007.04.008
  37. Shinkawa T, Nakamura K, Yamane N, Shoji-Hosaka E, Kanda Y, Sakurada M, Uchida K, Anazawa H, Satoh M, Yamasaki M, Hanai N, Shitara K (2003) The absence of fucose but not the presence of galactose or bisecting N-acetylglucosamine of human IgG1 complex-type oligosaccharides shows the critical role of enhancing antibody-dependent cellular cytotoxicity. J Biol Chem 278:3466-3473 https://doi.org/10.1074/jbc.M210665200
  38. Strasser R, Stadlmann J, Schähs M, Stiegler G, Quendler H, Mach L, Glossl J, Weterings K, Pabst M, Steinkellner H (2008) Generation of glyco-engineered Nicotiana benthamiana for the production of monoclonal antibodies with a homogeneous human-like N-glycan structure. Plant Biotechnol J 6:392-402 https://doi.org/10.1111/j.1467-7652.2008.00330.x
  39. Tangvoranuntakul P, Gagneux P, Diaz S, Bardor M, Varki N, Varki A, Muchmore E (2003) Human uptake and incorporation of an immunogenic nonhuman dietary sialic acid. Proc Natl Acad Sci USA 100:12045-12050 https://doi.org/10.1073/pnas.2131556100
  40. Umana P, Gagneux P, Diaz S, Bardor M, Varki N, Varki A, Muchmore E (1999) Engineered glycoforms of an antineuroblastoma IgG1 with optimized antibody-dependent cellular cytotoxic activity. Nat Biotechnol 17:176-180 https://doi.org/10.1038/6179

Cited by

  1. Features and applications of bacterial sialidases vol.91, pp.1, 2011, https://doi.org/10.1007/s00253-011-3307-2