Biochemical and biophysical characterization of humanized IgG1 produced in Pichia pastoris

mAbs

Volumn 3, Issue 5, 2011, Pages 453-460

  Ha, Sha ^a   Wang, Yang ^a   Rustandi, Richard R ^a  

^a MERCK RESEARCH LABORATORIES   (United States)

Author keywords

Analytical characterization; IgG; N linked glycan; O linked glycan; Pichia pastoris

Indexed keywords

GLYCAN; IMMUNOGLOBULIN G1; MANNOSE; METHIONINE;

CAPILLARY ELECTROPHORESIS; CHO CELL; DIFFERENTIAL SCANNING CALORIMETRY; GEL PERMEATION CHROMATOGRAPHY; GLYCOSYLATION; NONHUMAN; OXIDATION; PICHIA PASTORIS; POLYACRYLAMIDE GEL ELECTROPHORESIS; PROTEIN SECONDARY STRUCTURE; PROTEIN TERTIARY STRUCTURE; REVIEW; THERMOSTABILITY;

ANIMALS; ANTIBODY-DEPENDENT CELL CYTOTOXICITY; CHO CELLS; CRICETINAE; GLYCOSYLATION; HUMANS; IMMUNOGLOBULIN G; PICHIA; PROTEIN ENGINEERING; RECOMBINANT PROTEINS;

EID: 80052598704     PISSN: 19420862     EISSN: 19420870     Source Type: Journal    
DOI: 10.4161/mabs.3.5.16891     Document Type: Review

References (83)

1. Wood CR, Boss MA, Kenten JH, Calvert JE, Roberts NA. The synthesis and in vivo assembly of functional antibodies in yeast. Nature 1985; 314:446-9.
2. Horwitz AH, Chang CP, Better M, Hellstrom KE, Robinson RR. Secretion of functional antibody and Fab fragment from yeast cells. Proc Natl Acad Sci USA 1988; 85:8678-82.
3. Ogunjimi AA, Chandler JM, Gooding CM, Recinos A, Choudary PV. High-level secretory expression of immunologically active intact antibody from the yeast Pichia pastoris. Biotechnol Lett 1999; 21:561-7.
4. Ridder R, Schmitz R, Legay F, Gram H. Generation of rabbit monoclonal antibody fragments from a combinatorial phage display library and their production in the yeast Pichia pastoris. Nature Biotechnol 1995; 13:255-60.
5. Luo D, Mah N, Krantz M, Wilde K, Wishart D, Zhang Y, et al. VI-linker-Vh orientation-dependent expression of single chain Fv containing an engineered disulfide-stabilized bond in the framework regions. J Biochem 1995; 118:825-31.
6. Ando K, Arunwanich P, Kai K, Shinkai M, Honda H, Kobayashi T. Production of Fv fragment of monoclonal antibody from recombinant methylotrophic yeast, Pichia pastoris. J Chem Eng Jpn 1996; 29:390-2.
7. Luo D, Geng M, Noujaim AA, Madiyalakan R. An engineered bivalent single-chain antibody fragment that increases antigen binding activity. J Bicohem 1997; 121:831-4.
8. Luo D, Mah N, Krantz M, Wishart D, Jacobs F, Martin L. High level secretion of single-chain antibody in Pichia exression system. Biotechnol Tech 1997; 11:759-61.
9. Goel A, Beresford GW, Colcher D, Pavlinkova G, Booth BJM, Baranowska-Kortylewicz J, et al. Divalent forms of CC49 single-chain antibody constructs in Pichia pastoris: expression, purification and characterization. J Biochem 2000; 127:829-36.
10. Andrade EV, Albuquerque FC, Moraes LMP, Brigido MM, Santos-Silva MA. Single-chain Fv with Fc fragment of the human IgG1 tag: construction, Pichia pastoris expression and antigen binding characterization. J Biochem 2000; 128:891-5.
11. Freyre FM, Vazquez JE, Ayala M, Canaan-Haden L, Bell H, Rodriguez I, et al. Very high expression of an anti-carcinoembryonic antigen single chain Fv antibody fragment in the yeast Pichia pastoris. J Biotechnol 2000; 76:157-63.
12. Takahashi K, Yuuki T, Takai T, Ra C, Okumura K, Yokota T, et al. Production of humanized Fab fragment against human high affinity IgE receptor in Pichia pastoris. Biosci Biotechnol Biochem 2000; 64:2138-44.
13. Wang Y, Wang K, Jette DC, Wishart DS. Production of an anti-prostate-specific antigen single-chain antibody fragment from Pichia pastoris. Protein Expres Purif 2001; 23:419-25.
14. Lange S, Schmitt J, Schmid RD. High-yield expression of the recombinant, atrazine-specific Fab fragment K411B by the methylotrophic yeast Pichia pastoris. J Immunol Methods 2001; 255:103-14.
15. Shapiro RI, Wen D, Levesque M, Hronowski X, Gill A, Garber EA, et al. Expression of sonic hedgehog-Fc fusion protein in Pichia pastorsi. Identification and control of post-translational, chemical and proteolytic modifications. Protein Expres Purif 2003; 29:272-83.
16. Hu S, Li L, Qiao J, Guo Y, Cheng L, Liu J. Codon optimization, expression and characterization of an internalizing anti-ErbB2 single-chain antibody in Pichia pastoris. Protein Expres Purif 2006; 47:249-57.
17. Tanfous NGB, Kallel H, Jarboui MA, Fathallah DM. Expression in Pichia pastoris of a recombinant scFv form of mAb 107, an anti human CD11b integrin antibody. Enzyme Microb Technol 2006; 38:636-42.
18. Gasser B, Maurer M, Gach J, Kunert R, Mattanovich D. Engineering of Pichia pastoris for improved production of antibody fragments. Biotechnol Bioeng 2006; 94:353-61.
19. Lin H, Kim T, Xiong F, Yang X. Enhancing the production of Fc fusion protein in fed-batch fermentation Pichia pastoris by design of experiments. Biotechnol Prog 2007; 23:621-5.
20. Cai J, Li F, Wang SZ. Expression of secreted human single-chain fragment variable antibody against human amyloid beta peptide in Pichia patoris. Neural Regen Res 2008; 3:910-3.
21. Chang HJ, Choi SW, Chun HS. Expression of functional single-chain variable domain fragment antibody (scFv) against mycotoxin zearalenone in Pichia pastoris. Biotechnol Lett 2008; 30:1801-6.
22. Kunert R, Gach J, Katinger H. Expression of a Fab fragment in CHO and Pichia pastoris. BioProcess Int 2008; 6:34-6.
23. Schoonooghe S, Kaigorodov V, Zawisza M, Dumolyn C, Haustraete J, Grooten J, et al. Efficient production of human bivalent and trivalent anti-MUCI Fab-scFv antibodies in Pichia pastoris. BMC Biotechnol 2009; 9:70.
24. Callewaert N, Laroy W, Cadirgi H, Geysens S, Saelens X, Jou WM, Contreras R. Use of HDEL-tagged Trichoderma reesei mannosyl oligosaccharide 1,2-α-Dmannosidase for N-glycan engineering in Pichia pastoris. FEBS Lett 2001; 503:173-8.
25. Vervecken W, Kaigorodov V, Callewaert N, Geysens Vusser KD, Contreras R. In vivo synthesis of mammalian- like, hybrid-type N-glycans in Pichia pastoris. Appl Environ Microbiol 2004; 70:2639-46.
26. Choi BK, Bobrowicz P, Davidson RC, Hamilton SR, Kung DH, Li H, et al. Use of combinatorial genetic libraries to humanize N-linked glycosylation in the yeast Pichia pastoris. Proc Natl Acad Sci USA 2003; 100:5022-7.
27. Hamilton SR, Bobrowicz P, Bobrowicz B, Davidson RC, Li H, Mitchell T, et al. Production of complex human glycoproteins in yeast. Science 2003; 301:1244-6.
28. Bobrowicz P, Davidson RC, Li H, Potgieter TI, Nett JH, Hamilton SR, et al. Engineering of an artificial glycosylation pathway blocked in core oligosaccharide assembly in the yeast Pichia pastoris: production complex humanized glycoproteins with terminal galactose. Glycobiology 2004; 14:757-66.
29. Gerngross TU. Advances in the production of human therapeutic proteins in yeasts and filamentous fungi. Nature Biotechnol 2004; 22:1409-14.
30. Wildt S, Gerngross TU. The humanization N-glycosylation pathways in yeast. Nat Rev Microbiol 2005; 3:119-28.
31. Hamilton SR, Davidson RC, Sethuraman N, Nett JH, Jiang Y, Rios S, Bobrowicz P, et al. Humanization yeast to produce complex terminally sialylated glycoproteins. Science 2006; 313:1441-3.
32. Li H, Sethuraman N, Stadheim TA, Zha D, Prinz B, Ballew N, et al. Optimization of humanized IgGs glycoengineered Pichia pastoris. Nature Biotechnol 2006; 24:210-5.
33. Jacobs PP, Geysens S, Vervecken W, Contreras R, Callewaert N. Engineering complex-type N-glycosylation in pichia pastoris using GlycoSwitch technology. Nat Protocols 2009; 4:58-70.
34. Potgieter TI, Cukan M, Drummond JE, Houston-Cummings NR, Jiang Y, Li F, et al. Production monoclonal antibodies by glycoengineered Pichia pastoris. J Biotechnol 2009; 139:318-25.
35. Barnard GC, Kull AR, Sharkey NS, Shaikh SS, Rittenhour AM, Burnina I, et al. High-throughput screening and selection of yeast cell lines expressing monoclonal antibodies. J Ind Microbiol Biotechnol 2010; 37:961-71.
36. Jiang Y, Li F, Zha D, Potgieter T, Mitchell T, Moore R, et al. Purification process development of a recombinant monoclonal antibody expressed in glycoengineered Pichia pastoris. Protein Expr Purif 2011; 76:7-14.
37. Pinckard RN, Weir DM, McBride WH. Factors influencing the immune response. I. Effects of the physical state of the antigen and of lymphoreticular cell proliferation on the response to intravenous injection of bovine serum albumin in rabbits. Clin Exp Immunol 1967; 2:331-41.
38. Moore WV, Leppert P. Role of aggregated human growth hormone (hGH) in development of antibodies to hGH. J Clin Endocrinol Metabolism 1980; 51:691-7.
39. Robbins DC, Cooper SM, Fineberg SE, Mead PM. Antibodies to covalent aggregates of insulin in blood of insulin-using diabetic patients. Diabetes 1987; 36:838-41.
40. Frost H. Antibody-mediated side effects of recombinant proteins. Toxicology 2005; 209:155-60.
41. Arakawa T, Philo JS, Ejima D, Tsumoto K, Arisaka F. Aggregation analysis of therapeutic proteins, Part 1: General aspects and techniques for assessment. Bioprocess Int 2006; 4:32-43.
42. Arakawa T, Philo JS, Ejima D, Tsumoto K, Arisaka F. Aggregation analysis of therapeutic proteins, Part 2: Analytical Ultracentrifugation and dynamic light scattering. Bioprocess Int 2007; 5:36-50.
43. Krishnamurthy R, Sukumar M, Das TK, Lacher NA. Emerging analytical technologies for biotherapeutics development. BioProcess Int 2008; 6:32-43.
44. Cohen SL, Price C, Vlasak J. â-elimination and peptide bond hydrolysis: two distinct mechanisms of human IgG1 hinge fragmentation upon storage. J Am Chem Soc 2007; 129:6976-7.
45. Santora LC, Krull IS, Grant K. Characterization of recombinant human monoclonal tissue necrosis factor-α antibody using cation-exchange HPLC and capillary isoelectric focusing. Anal Biochem 1999; 275:98-108.
46. Harris RJ, Kabakoff B, Macchi FD, Shen FJ, Kwong M, Andya JD, et al. Identification of multiple sources of charge heterogeneity in a recombinant antibody. J Chrom B 2001; 752:233-45.
47. Mario N, Baudin B, Aussel C, Giboudeau J. Capillary isoelectric focusing and high-performance cationexchange chromatography compared for qualitative and quantitative analysis of hemoglobin variants. Clin Chem 1997; 43:2137-42.
48. Vlasak J, Bussat MC, Wang S, Wagner-Rousset E, Schaefer M, Klinguer-Hamour C, et al. Identification and characterization of asparagine deamidation in the light chain CDR1 of a humanized IgG1 antibody. Anal Biochem 2009; 392:145-54.
49. Li N, Kessler K, Bass L, Zeng D. Evaluation of the iCE280 Analyzer as a potential high-throughput tool for formulation development. J Pharm Biomed Anal 2007; 43:963-72.
50. Liu H, Gaza-Bulseco G, Xiang T, Chumsae C. Structural effect of deglycosylation and methionine oxidation on a recombinant monoclonal antibody. Mol Immunol 2008; 45:701-8.
51. Lam XM, Yang JY, Cleland JL. Antioxidants for prevention of methionine oxidation in recombinant monoclonal antibody HER2. J Pharm Sci 1997; 86:1250-5.
52. Chumsae C, Gaza-Bulseco G, Sun J, Liu H. Comparison of methionine oxidation in thermal stability and chemically stressed samples of a fully human monoclonal antibody. J Chromatogr B Analyt Technol Biomed Life Sci 2007; 850:285-94.
53. Bertolotti-Ciarlet A, Wang W, Lownes R, Pristatsky P, Fang Y, McKelvey T, et al. Impact of methionine oxidation on the binding of human IgG1 to FcRn and Fc γ receptors. Mol Immunol 2009; 46:1878-82.
54. Wang W, Vlasak J, Li Y, Pristatsky P, Fang Y, Pittman T, et al. Impact of methionine oxidation in human IgG1 Fc on serum half-life of monoclonal antibodies. Mol Immunol 2011; 48:860-6.
55. Pan H, Chen K, Chu L, Kinderman F, Apostol I, Huang G. Methionine oxidation in human IgG2 Fc decreases binding affinities to protein A and FcRn. Protein Sci 2009; 18:424-33.
56. Han M, Phan D, Nightlinger N, Taylor L, Jankhah S, Woodruff B, et al. Optimization of CE-SDS method for antibody separation based on multi-users experimental practices. Chromatographia 2006; 64:335-42.
57. Rustandi RR, Washabaugh MW, Wang Y. Applications of CE SDS gel in development of biopharmaceutical antibody-based products. Electrophoresis 2008; 29:3612-20.
58. Ha S, Ou Y, Vlasak J, Li Y, Wang S, Vo K, et al. Isolation and characterization of IgG1 with asymmetrical Fc glycosylation. Glycobiology 2011; 21:1087-96.
59. Huhn C, Selman MHJ, Ruhaak LR, Deelder AM, Wuhrer M. IgG glycosylation analysis. Proteomics 2009; 9:882-913.
60. Jefferis R. Glycosylation of recombinant antibody therapeutics. Biotechnol Prog 2005; 21:11-6.
61. Qian J, Liu T, Yang L, Daus A, Crowley R, Zhou Q. Structural characterization of N-linked oligosaccharides on monoclonal antibody cetuximab by the combination of orthogonal matrix-assisted laser desorption/ionization hybrid quadrupole-quadrupole time-of-flight tandem mass spectrometry and sequential enzymatic digestion. Anal Biochem 2007; 364:8-18.
62. Chung CH, Mirakhur B, Chan E, Le QT, Berlin J, Morse M, et al. Cetuximab-induced anaphylaxis and IgE specific for galactose-α-1,3- galactose. N Engl J Med 2008; 358:1109-17.
63. Li H, Miele RG, Mitchell TI, Gerngross TU. N-linked glycan characterization of heterologous proteins. Methods Mol Biol 2007; 389:139-50.
64. Gong B, Cukan M, Fisher R, Li H, Stadheim TA, Gerngross T. Characterization of N-linked glycosylation on recombinant glycoproteins produced in Pichia pastoris using ESI-MS and MALDI-TOF. In: Packer NH, Karlsson NG, Eds. Methods in Molecular Biology, Glycomics: Methods and Protocols. Humana Press 2009; 534:213-23.
65. Zhang N, Liu L, Dumitru CD, Cummings NRH, Cukan M, Jiang Y, et al. Glycoengineered Pichia produced anti-HER2 is comparable to trastuzumab in preclinical study. MAbs 2011; 3:289-98.
66. Ma S, Nashabeh W. Carbohydrate analysis of a chimeric recombinant monoclonal antibody by capillary electrophoresis with laser-induced fluorescence detection. Anal Chem 1999; 71:5185-92.
67. Liu Y, Salas-Solano O, Gennaro LA. Investigation of sample preparation artifacts formed during the enzymatic release of N-linked glycans prior to analysis by capillary electrophoresis. Anal Chem 2009; 81:6823-9.
68. Duman JG, Miele RG, Liang H, Grella DK, Sim KL, Castellino KJ, et al. O-mannosylation of Pichia pastoris cellular and recombinant proteins. Biotechnol Appl Biochem 1998; 28:39-45.
69. Chiba A, Matsumura K, Yamada H, Inazu T, Shimizu T, Kusunoki S, et al. Structures of sialylated O-linked oligosaccharides of bovine peripheral nerve alphadystroglycan. The role of a novel O-mannosyl-type oligosaccharide in the binding of alpha- dystroglycan with laminin. J Biol Chem 1997; 272:2156-62.
70. Sasaki T, Yamada H, Matsumura K, Shimizu T, Kobata A, Endo T. Detection of O-mannosyl glycans in rabbit skeletal muscle alpha-dystroglycan. Biochim Biophys Acta 1998; 1425:599-606.
71. Smalheiser NR, Haslam SM, Sutton-Smith M, Morris HR, Dell A. Structural analysis of sequences O-linked to mannose reveals a novel Lewis X structure in cranin (dystroglycan) purified from sheep brain. J Biol Chem 1998; 273:23698-703.
72. Lommel M, Strahl S. Protein O-mannosylation: conserved from bacteria to humans. Glycobiology 2009; 19:816-28.
73. Barresi R, Campbell KP. Dystroglycan: from biosynthesis to pathogenesis of human disease. J Cell Sci 2006; 119:199-207.
74. Kim H, Yamaguchi Y, Masuda K, Matsunaga C, Yamamoto K, Irimura T, et al. O-glycosylation in hinge region of mouse immunoglobin G2b. J Biol Chem 1994; 269:12345-50.
75. Arnold JN, Radcliffe CM, Wormald MR, Royle L, Harvey DJ, Crispin M, et al. The glycosylation of human serum IgD and IgE and the accessibility of identified oligomannose structures for interaction with mannan-binding lectin. J Immunol 2004; 173:6831-40.
76. Martinez T, Pace D, Brady L, Gerhart M, Balland A. Characterization of a novel modification on IgG2 light chain evidence for the presence of O-linked mannosylation. J Chrom A 2007; 1156:183-7.
77. Girrbach V, Strahl S. Members of the evolutionarily conserved PMT family of protein O-mannosyltransferases form distinct protein complexes among themselves. J Biol Chem 2003; 278:12554-62.
78. Kuroda K, Kobayashi K, Kitagawa Y, Nakagawa T, Tsumura H, Komeda T, et al. Efficient antibody production upon suppression of O mannosylation in the yeast Ogataea minuta. Appl Environ Microbiol 2008; 74:446-53.
79. Stadheim TA, Li H, Kett W, Burnina IN, Gerngross TU. Use of high-performance anion exchange chromatography with pulsed amperometric detection for O-glycan determination in yeast. Nat Protocols 2008; 3:1026-31.
80. Wang S, Ionescu R, Peekhaus N, Leung J, Ha S, Vlasak J. Separation of post-translational modifications in monoclonal antibodies by exploiting subtle conformational changes under mildly acidic conditions. J Chrom A 2010; 1217:6496-502.
81. Ionescu R, Vlasak J, Price C, Kirchmeier M. Contribution of variable domains to the stability of humanized IgG1 monoclonal antibodies. J Pharm Sci 2008; 97:1414-26.
82. Shields RL, Lai J, Keck R, O'Connell LY, Hong K, Meng YG, et al. Lack of fucose on human IgG1 N-linked oligosaccharide improves binding to human FcγRIII and antibody-dependent cellular toxicity. J Biol Chem 2002; 277:26733-40.
83. Suzuki E, Niwa R, Saji S, Muta M, Hirose M, Iida S, et al. A nonfucosylated anti-HER2 antibody augments antibody-dependent cellular cytotoxicity in breast cancer patients. Clin Cancer Res 2007; 13:1875-82.