Crystallizable fragment glycoengineering for therapeutic antibodies development

Frontiers in Immunology

Volumn 8, Issue NOV, 2017, Pages

  Li, Wei ^a   Zhu, Zhongyu ^a   Chen, Weizao ^a   Feng, Yang ^a   Dimitrov, Dimiter S ^a  

^a NATIONAL CANCER INSTITUTE   (United States)

Author keywords

Aglycosylated monoclonal antibodies; Antibody drug conjugate; Chemoenzymatic glycosylation remodeling; Crystallizable fragment glycoengineering; Crystallizable fragment glycosylation; Effector function; Homogenous glycoforms; Monoclonal antibodies

Indexed keywords

GALACTOSE; RITUXIMAB;

ANIMAL CELL; ANTIBODY DEPENDENT CELLULAR CYTOTOXICITY; CELL ENGINEERING; CHEMICAL REACTION; COMPLEMENT DEPENDENT CYTOTOXICITY; DNA MODIFICATION; IMMUNOGENICITY; NONHUMAN; PROTEIN CARBOHYDRATE INTERACTION; PROTEIN CONFORMATION; PROTEIN PROCESSING; PROTEIN STRUCTURE; PROTEIN SYNTHESIS; REVIEW; SIALYLATION;

EID: 85034020444     PISSN: None     EISSN: 16643224     Source Type: Journal    
DOI: 10.3389/fimmu.2017.01554     Document Type: Review

References (135)

1. Elvin JG, Couston RG, van der Walle CF. Therapeutic antibodies: market considerations, disease targets and bioprocessing. Int J Pharm (2013) 440:83-98. doi:10.1016/j.ijpharm.2011.12.039
2. Reichert JM. Antibodies to watch in 2017. MABs (2017) 9:167-81. doi:10.1080/19420862.2016.1269580
3. Niwa R, Satoh M. The current status and prospects of antibody engineering for therapeutic use: focus on glycoengineering technology. J Pharm Sci (2015) 104:930-41. doi:10.1002/jps.24316
4. Walsh G. Biopharmaceutical benchmarks 2014. Nat Biotechnol (2014) 32:992-1000. doi:10.1038/nbt.3040
5. Beck A, Wagner-Rousset E, Bussat MC, Lokteff M, Klinguer-Hamour C, Haeuw JF, et al. Trends in glycosylation, glycoanalysis and glycoengineering of therapeutic antibodies and Fc-fusion proteins. Curr Pharm Biotechnol (2008) 9:482-501. doi:10.2174/138920108786786411
6. Jefferis R. Glycosylation of recombinant antibody therapeutics. Biotechnol Prog (2005) 21:11-6. doi:10.1021/bp040016j
7. Jefferis R. Glycosylation as a strategy to improve antibody-based therapeutics. Nat Rev Drug Discov (2009) 8:226-34. doi:10.1038/nrd2804
8. Liu L. Pharmacokinetics of monoclonal antibodies and Fc-fusion proteins. Protein cell (2017). doi:10.1007/s13238-017-0408-4
9. Liu L. Antibody glycosylation and its impact on the pharmacokinetics and pharmacodynamics of monoclonal antibodies and Fc-fusion proteins. J Pharm Sci (2015) 104:1866-84. doi:10.1002/jps.24444
10. Liu H, Nowak C, Andrien B, Shao M, Ponniah G, Neill A. Impact of IgG Fc-oligosaccharides on recombinant monoclonal antibody structure, stability, safety, and efficacy. Biotechnol Prog (2017) 33(5):1173-81. doi:10.1002/btpr.2498
11. Bournazos S, Wang TT, Dahan R, Maamary J, Ravetch JV. Signaling by antibodies: recent progress. Annu Rev Immunol (2017) 35:285-311. doi:10.1146/annurev-immunol-051116-052433
12. Quast I, Peschke B, Lunemann JD. Regulation of antibody effector functions through IgG Fc N-glycosylation. Cell Mol Life Sci (2017) 74:837-47. doi:10.1007/s00018-016-2366-z
13. Le NP, Bowden TA, Struwe WB, Crispin M. Immune recruitment or suppression by glycan engineering of endogenous and therapeutic antibodies. Biochim Biophys Acta (2016) 1860:1655-68. doi:10.1016/j.bbagen.2016.04.016
14. Raju TS. Terminal sugars of Fc glycans influence antibody effector functions of IgGs. Curr Opin Immunol (2008) 20:471-8. doi:10.1016/j.coi.2008.06.007
15. Subedi GP, Barb AW. The structural role of antibody N-glycosylation in receptor interactions. Structure (2015) 23:1573-83. doi:10.1016/j.str.2015.06.015
16. Brader ML, Estey T, Bai S, Alston RW, Lucas KK, Lantz S, et al. Examination of thermal unfolding and aggregation profiles of a series of developable therapeutic monoclonal antibodies. Mol Pharm (2015) 12:1005-17. doi:10.1021/mp400666b
17. Mimura Y, Church S, Ghirlando R, Ashton PR, Dong S, Goodall M, et al. The influence of glycosylation on the thermal stability and effector function expression of human IgG1-Fc: properties of a series of truncated glycoforms. Mol Immunol (2000) 37:697-706. doi:10.1016/S0161-5890(00)00105-X
18. Feige MJ, Walter S, Buchner J. Folding mechanism of the CH2 antibody domain. J Mol Biol (2004) 344:107-18. doi:10.1016/j.jmb.2004.09.033
19. Zheng K, Bantog C, Bayer R. The impact of glycosylation on monoclonal antibody conformation and stability. MABs (2011) 3:568-76. doi:10.4161/mabs.3.6.17922
20. Krapp S, Mimura Y, Jefferis R, Huber R, Sondermann P. Structural analysis of human IgG-Fc glycoforms reveals a correlation between glycosylation and structural integrity. J Mol Biol (2003) 325:979-89. doi:10.1016/S0022-2836(02)01250-0
21. Tao MH, Morrison SL. Studies of aglycosylated chimeric mouse-human IgG. Role of carbohydrate in the structure and effector functions mediated by the human IgG constant region. J Immunol (1989) 143:2595-601
22. Raju TS, Scallon B. Fc glycans terminated with N-acetylglucosamine residues increase antibody resistance to papain. Biotechnol Prog (2007) 23:964-71. doi:10.1021/bp070118k
23. Raju TS, Scallon BJ. Glycosylation in the Fc domain of IgG increases resistance to proteolytic cleavage by papain. Biochem Biophys Res Commun (2006) 341:797-803. doi:10.1016/j.bbrc.2006.01.030
24. Raju TS, Briggs JB, Chamow SM, Winkler ME, Jones AJ. Glycoengineering of therapeutic glycoproteins: in vitro galactosylation and sialylation of glycoproteins with terminal N-acetylglucosamine and galactose residues. Biochemistry (2001) 40:8868-76. doi:10.1021/bi010475i
25. Jones AJ, Papac DI, Chin EH, Keck R, Baughman SA, Lin YS, et al. Selective clearance of glycoforms of a complex glycoprotein pharmaceutical caused by terminal N-acetylglucosamine is similar in humans and cynomolgus monkeys. Glycobiology (2007) 17:529-40. doi:10.1093/glycob/cwm017
26. Goetze AM, Liu YD, Zhang Z, Shah B, Lee E, Bondarenko PV, et al. High-mannose glycans on the Fc region of therapeutic IgG antibodies increase serum clearance in humans. Glycobiology (2011) 21:949-59. doi:10.1093/glycob/cwr027
27. Wright A, Sato Y, Okada T, Chang K, Endo T, Morrison S. In vivo trafficking and catabolism of IgG1 antibodies with Fc associated carbohydrates of differing structure. Glycobiology (2000) 10:1347-55. doi:10.1093/glycob/10.12.1347
28. Ghaderi D, Taylor RE, Padler-Karavani V, Diaz S, Varki A. Implications of the presence of N-glycolylneuraminic acid in recombinant therapeutic glycoproteins. Nat Biotechnol (2010) 28:863-7. doi:10.1038/nbt.1651
29. Chung CH, Mirakhur B, Chan E, Le QT, Berlin J, Morse M, et al. Cetuximab-induced anaphylaxis and IgE specific for galactose-alpha-1, 3-galactose. N Engl J Med (2008) 358:1109-17. doi:10.1056/NEJMoa074943
30. Reusch D, Tejada ML. Fc glycans of therapeutic antibodies as critical quality attributes. Glycobiology (2015) 25:1325-34. doi:10.1093/glycob/cwv065
31. Dicker M, Strasser R. Using glyco-engineering to produce therapeutic proteins. Expert Opin Biol Ther (2015) 15:1501-16. doi:10.1517/14712598.2015.1069271
32. Costa AR, Rodrigues ME, Henriques M, Oliveira R, Azeredo J. Glycosylation: impact, control and improvement during therapeutic protein production. Crit Rev Biotechnol (2014) 34:281-99. doi:10.3109/07388551.2013.793649
33. Jefferis R. Isotype and glycoform selection for antibody therapeutics. Arch Biochem Biophys (2012) 526:159-66. doi:10.1016/j.abb.2012.03.021
34. Mimura Y, Katoh T, Saldova R, O'Flaherty R, Izumi T, Mimura-Kimura Y, et al. Glycosylation engineering of therapeutic IgG antibodies: challenges for the safety, functionality and efficacy. Protein Cell (2017). doi:10.1007/s13238-017-0433-3
35. Hale G, Rebello P, Al Bakir I, Bolam E, Wiczling P, Jusko WJ, et al. Pharmacokinetics and antibody responses to the CD3 antibody otelixizumab used in the treatment of type 1 diabetes. J Clin Pharmacol (2010) 50:1238-48. doi:10.1177/0091270009356299
36. Ng CM, Stefanich E, Anand BS, Fielder PJ, Vaickus L. Pharmacokinetics/pharmacodynamics of nondepleting anti-CD4 monoclonal antibody (TRX1) in healthy human volunteers. Pharm Res (2006) 23:95-103. doi:10.1007/s11095-005-8814-3
37. Ishida T, Joh T, Uike N, Yamamoto K, Utsunomiya A, Yoshida S, et al. Defucosylated anti-CCR4 monoclonal antibody (KW-0761) for relapsed adult T-cell leukemia-lymphoma: a multicenter phase II study. J Clin Oncol (2012) 30:837-42. doi:10.1200/JCO.2011.37.3472
38. Duvic M, Pinter-Brown L, Foss FM, Sokol L, Jorgensen J, Spitalny GL, et al. Results of a phase 1/2 study for KW-0761, a monoclonal antibody directed against CC chemokine receptor type 4 (CCR4), in CTCL patients. Blood (2010) 116:962-962
39. Camacho LH, Joyce R, Brown JR, Chanan-Khan A, Amrein PC, Assad A, et al. A phase 1, open-label, multi-center, multiple-dose, dose-escalation study of MDX-1342 in patients with CD19-positive refractory/relapsed chronic lymphocytic leukemia. Blood (2009) 114:3425-3425
40. Goede V, Fischer K, Busch R, Engelke A, Eichhorst B, Wendtner CM, et al. Obinutuzumab plus chlorambucil in patients with CLL and coexisting conditions. N Engl J Med (2014) 370:1101-10. doi:10.1056/NEJMoa1313984
41. Yu X, Marshall MJE, Cragg MS, Crispin M. Improving antibody-based cancer therapeutics through glycan engineering. BioDrugs (2017) 31:151-66. doi:10.1007/s40259-017-0223-8
42. Paz-Ares LG, Gomez-Roca C, Delord JP, Cervantes A, Markman B, Corral J, et al. Phase I pharmacokinetic and pharmacodynamic dose-escalation study of RG7160 (GA201), the first glycoengineered monoclonal antibody against the epidermal growth factor receptor, in patients with advanced solid tumors. J Clin Oncol (2011) 29:3783-90. doi:10.1200/JCO.2011.34.8888
43. Hristodorov D, Fischer R, Linden L. With or without sugar? (A)glycosylation of therapeutic antibodies. Mol Biotechnol (2013) 54:1056-68. doi:10.1007/s12033-012-9612-x
44. Peschke B, Keller CW, Weber P, Quast I, Lunemann JD. Fc-galactosylation of human immunoglobulin gamma isotypes improves C1q binding and enhances complement-dependent cytotoxicity. Front Immunol (2017) 8:646. doi:10.3389/fimmu.2017.00646
45. Li H, Sethuraman N, Stadheim TA, Zha D, Prinz B, Ballew N, et al. Optimization of humanized IgGs in glycoengineered Pichia pastoris. Nat Biotechnol (2006) 24:210-5. doi:10.1038/nbt1178
46. Liu B, Gong X, Chang S, Yang Y, Song M, Duan D, et al. Disruption of the OCH1 and MNN1 genes decrease N-glycosylation on glycoprotein expressed in Kluyveromyces lactis. J Biotechnol (2009) 143:95-102. doi:10.1016/j.jbiotec.2009.06.016
47. Davidson RC, Nett JH, Renfer E, Li H, Stadheim TA, Miller BJ, et al. Functional analysis of the ALG3 gene encoding the Dol-P-Man: Man5GlcNAc2-PP-Dol mannosyltransferase enzyme of P. pastoris. Glycobiology (2004) 14:399-407. doi:10.1093/glycob/cwh023
48. Castilho A, Bohorova N, Grass J, Bohorov O, Zeitlin L, Whaley K, et al. Rapid high yield production of different glycoforms of Ebola virus monoclonal antibody. PLoS One (2011) 6:e26040. doi:10.1371/journal.pone.0026040
49. Davey RT Jr, Dodd L, Proschan MA, Neaton J, Neuhaus Nordwall J, Koopmeiners JS, et al. A randomized, controlled trial of ZMapp for Ebola virus infection. N Eng J Med (2016) 375:1448-56. doi:10.1056/NEJMoa1604330
50. Urbain R, Teillaud JL, Prost JF. [EMABling antibodies: from feto-maternal allo-immunisation prophylaxis to chronic lymphocytic leukaemia therapy]. Med Sci (Paris) (2009) 25:1141-4. doi:10.1051/medsci/200925121141
51. 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 Fcgamma RIII and antibody-dependent cellular toxicity. J Biol Chem (2002) 277:26733-40. doi:10.1074/jbc.M202069200
52. Gardai SJ, Epp A, Linares G, Westendorf L, Sutherland MK, Neff-LaFord H, et al. A sugar engineered non-fucosylated anti-CD40 antibody, SEA-CD40, with enhanced immune stimulatory activity alone and in combination with immune checkpoint inhibitors. J Clin Oncol (2015) 33:3074-3074. doi:10.1200/jco.2015.33.15_suppl.3074
53. Kanda Y, Imai-Nishiya H, Kuni-Kamochi R, Mori K, Inoue M, Kitajima-Miyama K, et al. Establishment of a GDP-mannose 4, 6-dehydratase (GMD) knockout host cell line: a new strategy for generating completely non-fucosylated recombinant therapeutics. J Biotechnol (2007) 130:300-10. doi:10.1016/j.jbiotec.2007.04.025
54. von Horsten HH, Ogorek C, Blanchard V, Demmler C, Giese C, Winkler K, et al. Production of non-fucosylated antibodies by co-expression of heterologous GDP-6-deoxy-d-lyxo-4-hexulose reductase. Glycobiology (2010) 20:1607-18. doi:10.1093/glycob/cwq109
55. Bardhi A, Wu Y, Chen W, Zhu Z, Zheng JH, Wong H, et al. Potent in vivo NK cell-mediated elimination of HIV-1-infected cells mobilized by a gp120-bispecific and hexavalent broadly neutralizing fusion protein. J Virol (2017) 91(20):e937-917. doi:10.1128/JVI.00937-17
56. Chen W, Bardhi A, Feng Y, Wang Y, Qi Q, Li W, et al. Improving the CH1-CK heterodimerization and pharmacokinetics of 4Dm2m, a novel potent CD4-antibody fusion protein against HIV-1. MABs (2016) 8:761-74. doi:10.1080/19420862.2016.1160180
57. Robak T, Robak E. New anti-CD20 monoclonal antibodies for the treatment of B-cell lymphoid malignancies. BioDrugs (2011) 25:13-25. doi:10.2165/11539590-000000000-00000
58. Mirschberger C, Schiller CB, Schraml M, Dimoudis N, Friess T, Gerdes CA, et al. RG7116, a therapeutic antibody that binds the inactive HER3 receptor and is optimized for immune effector activation. Cancer Res (2013) 73:5183-94. doi:10.1158/0008-5472.CAN-13-0099
59. Mori K, Kuni-Kamochi R, Yamane-Ohnuki N, Wakitani M, Yamano K, Imai H, et al. Engineering Chinese hamster ovary cells to maximize effector function of produced antibodies using FUT8 siRNA. Biotechnol Bioeng (2004) 88:901-8. doi:10.1002/bit.20326
60. Imai-Nishiya H, Mori K, Inoue M, Wakitani M, Iida S, Shitara K, et al. Double knockdown of alpha1, 6-fucosyltransferase (FUT8) and GDP-mannose 4, 6-dehydratase (GMD) in antibody-producing cells: a new strategy for generating fully non-fucosylated therapeutic antibodies with enhanced ADCC. BMC Biotechnol (2007) 7:84. doi:10.1186/1472-6750-7-84
61. Matsushita T. Engineered therapeutic antibodies with enhanced effector functions: clinical application of the Potelligent(R) Technology. Korean J Hematol (2011) 46:148-50. doi:10.5045/kjh.2011.46.3.148
62. Yamane-Ohnuki N, Kinoshita S, Inoue-Urakubo M, Kusunoki M, Iida S, Nakano R, et al. Establishment of FUT8 knockout Chinese hamster ovary cells: an ideal host cell line for producing completely defucosylated antibodies with enhanced antibody-dependent cellular cytotoxicity. Biotechnol Bioeng (2004) 87:614-22. doi:10.1002/bit.20151
63. Chen W, Feng Y, Prabakaran P, Ying T, Wang Y, Sun J, et al. Exceptionally potent and broadly cross-reactive, bispecific multivalent HIV-1 inhibitors based on single human CD4 and antibody domains. J Virol (2014) 88:1125-39. doi:10.1128/JVI.02566-13
64. Zhang P, Woen S, Wang T, Liau B, Zhao S, Chen C, et al. Challenges of glycosylation analysis and control: an integrated approach to producing optimal and consistent therapeutic drugs. Drug Discov Today (2016) 21:740-65. doi:10.1016/j.drudis.2016.01.006
65. Nagae M, Yamaguchi Y. Function and 3D structure of the N-glycans on glycoproteins. Int J Mol Sci (2012) 13:8398-429. doi:10.3390/ijms13078398
66. Wormald MR, Rudd PM, Harvey DJ, Chang SC, Scragg IG, Dwek RA. Variations in oligosaccharide-protein interactions in immunoglobulin G determine the site-specific glycosylation profiles and modulate the dynamic motion of the Fc oligosaccharides. Biochemistry (1997) 36:1370-80. doi:10.1021/bi9621472
67. Jefferis R. Recombinant antibody therapeutics: the impact of glycosylation on mechanisms of action. Trends Pharmacol Sci (2009) 30:356-62. doi:10.1016/j.tips.2009.04.007
68. Zauner G, Selman MHJ, Bondt A, Rombouts Y, Blank D, Deelder AM, et al. Glycoproteomic analysis of antibodies. Mol Cell Proteomics (2013) 12:856-65. doi:10.1074/mcp.R112.026005
69. Wuhrer M, Stam JC, van de Geijn FE, Koeleman CA, Verrips CT, Dolhain RJ, et al. Glycosylation profiling of immunoglobulin G (IgG) subclasses from human serum. Proteomics (2007) 7:4070-81. doi:10.1002/pmic.200700289
70. Raju TS, Briggs JB, Borge SM, Jones AJ. Species-specific variation in glycosylation of IgG: evidence for the species-specific sialylation and branch-specific galactosylation and importance for engineering recombinant glycoprotein therapeutics. Glycobiology (2000) 10:477-86. doi:10.1093/glycob/10.5.477
71. Butters TD. Control in the N-linked glycoprotein biosynthesis pathway. Chem Biol (2002) 9:1266-8. doi:10.1016/S1074-5521(02)00290-9
72. Brooks SA. Appropriate glycosylation of recombinant proteins for human use: implications of choice of expression system. Mol Biotechnol (2004) 28:241-55. doi:10.1385/MB:28:3:241
73. Girardi E, Holdom MD, Davies AM, Sutton BJ, Beavil AJ. The crystal structure of rabbit IgG-Fc. Biochem J (2009) 417:77-83. doi:10.1042/BJ20081355
74. Matsumiya S, Yamaguchi Y, Saito J, Nagano M, Sasakawa H, Otaki S, et al. Structural comparison of fucosylated and nonfucosylated Fc fragments of human immunoglobulin G1. J Mol Biol (2007) 368:767-79. doi:10.1016/j.jmb.2007.02.034
75. Kiyoshi M, Tsumoto K, Ishii-Watabe A, Caaveiro JMM. Glycosylation of IgG-Fc: a molecular perspective. Int Immunol (2017) 29(7):311-7. doi:10.1093/intimm/dxx038
76. Chiang AW, Li S, Spahn PN, Richelle A, Kuo CC, Samoudi M, et al. Modulating carbohydrate-protein interactions through glycoengineering of monoclonal antibodies to impact cancer physiology. Curr Opin Struct Biol (2016) 40:104-11. doi:10.1016/j.sbi.2016.08.008
77. Raju TS, Lang SE. Diversity in structure and functions of antibody sialylation in the Fc. Curr Opin Biotechnol (2014) 30:147-52. doi:10.1016/j.copbio.2014.06.014
78. Bologna L, Gotti E, Manganini M, Rambaldi A, Intermesoli T, Introna M, et al. Mechanism of action of type II, glycoengineered, anti-CD20 monoclonal antibody GA101 in B-chronic lymphocytic leukemia whole blood assays in comparison with rituximab and alemtuzumab. J Immunol (2011) 186:3762-9. doi:10.4049/jimmunol.1000303
79. Ferrara C, Grau S, Jager C, Sondermann P, Brunker P, Waldhauer I, et al. Unique carbohydrate-carbohydrate interactions are required for high affinity binding between FcgammaRIII and antibodies lacking core fucose. Proc Natl Acad Sci U S A (2011) 108:12669-74. doi:10.1073/pnas.1108455108
80. Mizushima T, Yagi H, Takemoto E, Shibata-Koyama M, Isoda Y, Iida S, et al. Structural basis for improved efficacy of therapeutic antibodies on defucosylation of their Fc glycans. Genes Cells (2011) 16:1071-80. doi:10.1111/j.1365-2443.2011.01552.x
81. Iida S, Misaka H, Inoue M, Shibata M, Nakano R, Yamane-Ohnuki N, et al. Nonfucosylated therapeutic IgG1 antibody can evade the inhibitory effect of serum immunoglobulin G on antibody-dependent cellular cytotoxicity through its high binding to FcgammaRIIIa. Clin Cancer Res (2006) 12:2879-87. doi:10.1158/1078-0432.CCR-05-2619
82. Iida S, Kuni-Kamochi R, Mori K, Misaka H, Inoue M, Okazaki A, et al. Two mechanisms of the enhanced antibody-dependent cellular cytotoxicity (ADCC) efficacy of non-fucosylated therapeutic antibodies in human blood. BMC Cancer (2009) 9:58. doi:10.1186/1471-2407-9-58
83. Niwa R, Hatanaka S, Shoji-Hosaka E, Sakurada M, Kobayashi Y, Uehara A, et al. Enhancement of the antibody-dependent cellular cytotoxicity of low-fucose IgG1 is independent of FcgammaRIIIa functional polymorphism. Clin Cancer Res (2004) 10:6248-55. doi:10.1158/1078-0432.CCR-04-0850
84. Weng W-K, Levy R. Two immunoglobulin G fragment C receptor polymorphisms independently predict response to rituximab in patients with follicular lymphoma. J Clin Oncol (2003) 21:3940-7. doi:10.1200/JCO.2003.05.013
85. Shibata-Koyama M, Iida S, Misaka H, Mori K, Yano K, Shitara K, et al. Nonfucosylated rituximab potentiates human neutrophil phagocytosis through its high binding for FcgammaRIIIb and MHC class II expression on the phagocytotic neutrophils. Exp Hematol (2009) 37:309-21. doi:10.1016/j.exphem.2008.11.006
86. Hodoniczky J, Zheng YZ, James DC. Control of recombinant monoclonal antibody effector functions by Fc N-glycan remodeling in vitro. Biotechnol Prog (2005) 21:1644-52. doi:10.1021/bp050228w
87. Starovasnik MA, Braisted AC, Wells JA. Structural mimicry of a native protein by a minimized binding domain. Proc Natl Acad Sci U S A (1997) 94:10080-5. doi:10.1073/pnas.94.19.10080
88. Sauer-Eriksson AE, Kleywegt GJ, Uhlen M, Jones TA. Crystal structure of the C2 fragment of streptococcal protein G in complex with the Fc domain of human IgG. Structure (1995) 3:265-78. doi:10.1016/S0969-2126(01)00157-5
89. Ghirlando R, Lund J, Goodall M, Jefferis R. Glycosylation of human IgG-Fc: influences on structure revealed by differential scanning micro-calorimetry. Immunol Lett (1999) 68:47-52. doi:10.1016/S0165-2478(99)00029-2
90. Raju TS, Davidson EA. Role of sialic acid on the viscosity of canine tracheal mucin glycoprotein. Biochem Biophys Res Commun (1994) 205:402-9. doi:10.1006/bbrc.1994.2679
91. Crispin M, Yu X, Bowden TA. Crystal structure of sialylated IgG Fc: implications for the mechanism of intravenous immunoglobulin therapy. Proc Natl Acad Sci U S A (2013) 110:E3544-6. doi:10.1073/pnas.1310657110
92. Fang J, Richardson J, Du Z, Zhang Z. Effect of Fc-Glycan structure on the conformational stability of IgG revealed by hydrogen/deuterium exchange and limited proteolysis. Biochemistry (2016) 55:860-8. doi:10.1021/acs.biochem.5b01323
93. Scallon BJ, Tam SH, McCarthy SG, Cai AN, Raju TS. Higher levels of sialylated Fc glycans in immunoglobulin G molecules can adversely impact functionality. Mol Immunol (2007) 44:1524-34. doi:10.1016/j.molimm.2006.09.005
94. Sondermann P, Kaiser J, Jacob U. Molecular basis for immune complex recognition: a comparison of Fc-receptor structures. J Mol Biol (2001) 309:737-49. doi:10.1006/jmbi.2001.4670
95. Kaneko Y, Nimmerjahn F, Ravetch JV. Anti-inflammatory activity of immunoglobulin G resulting from Fc sialylation. Science (2006) 313:670-3. doi:10.1126/science.1129594
96. Anthony RM, Nimmerjahn F, Ashline DJ, Reinhold VN, Paulson JC, Ravetch JV. Recapitulation of IVIG anti-inflammatory activity with a recombinant IgG Fc. Science (2008) 320:373-6. doi:10.1126/science.1154315
97. Anthony RM, Ravetch JV. A novel role for the IgG Fc glycan: the anti-inflammatory activity of sialylated IgG Fcs. J Clin Immunol (2010) 30(Suppl 1):S9-14. doi:10.1007/s10875-010-9405-6
98. Anthony RM, Kobayashi T, Wermeling F, Ravetch JV. Intravenous gammaglobulin suppresses inflammation through a novel T(H)2 pathway. Nature (2011) 475:110-3. doi:10.1038/nature10134
99. Yamane-Ohnuki N, Satoh M. Production of therapeutic antibodies with controlled fucosylation. MABs (2009) 1:230-6. doi:10.4161/mabs.1.3.8328
100. Crowell CK, Grampp GE, Rogers GN, Miller J, Scheinman RI. Amino acid and manganese supplementation modulates the glycosylation state of erythropoietin in a CHO culture system. Biotechnol Bioeng (2007) 96:538-49. doi:10.1002/bit.21141
101. Patel TP, Parekh RB, Moellering BJ, Prior CP. Different culture methods lead to differences in glycosylation of a murine IgG monoclonal antibody. Biochem J (1992) 285(Pt 3):839-45. doi:10.1042/bj2850839
102. Okeley NM, Alley SC, Anderson ME, Boursalian TE, Burke PJ, Emmerton KM, et al. Development of orally active inhibitors of protein and cellular fucosylation. Proc Natl Acad Sci U S A (2013) 110:5404-9. doi:10.1073/pnas.1222263110
103. Powell LD. Inhibition of N-linked glycosylation. Curr Protoc Immunol. (2001) 9:8.14-1-9. doi:10.1002/0471142735.im0814s09
104. Sullivan FX, Kumar R, Kriz R, Stahl M, Xu GY, Rouse J, et al. Molecular cloning of human GDP-mannose 4, 6-dehydratase and reconstitution of GDP-fucose biosynthesis in vitro. J Biol Chem (1998) 273:8193-202. doi:10.1074/jbc.273.14.8193
105. King JD, Poon KKH, Webb NA, Anderson EM, McNally DJ, Brisson JR, et al. The structural basis for catalytic function of GMD and RMD, two closely related enzymes from the GDP-D-rhamnose biosynthesis pathway. FEBS J (2009) 276:2686-700. doi:10.1111/j.1742-4658.2009.06993.x
106. Son YD, Jeong YT, Park SY, Kim JH. Enhanced sialylation of recombinant human erythropoietin in Chinese hamster ovary cells by combinatorial engineering of selected genes. Glycobiology (2011) 21:1019-28. doi:10.1093/glycob/cwr034
107. Chan KF, Shahreel W, Wan C, Teo G, Hayati N, Tay SJ, et al. Inactivation of GDP-fucose transporter gene (Slc35c1) in CHO cells by ZFNs, TALENs and CRISPR-Cas9 for production of fucose-free antibodies. Biotechnol J (2016) 11:399-414. doi:10.1002/biot.201500331
108. Evans JB, Syed BA. From the analyst's couch: next-generation antibodies. Nat Rev Drug Discov (2014) 13:413-4. doi:10.1038/nrd4255
109. Ferrara C, Brunker P, Suter T, Moser S, Puntener U, Umana P. Modulation of therapeutic antibody effector functions by glycosylation engineering: influence of Golgi enzyme localization domain and co-expression of heterologous beta1, 4-N-acetylglucosaminyltransferase III and Golgi alpha-mannosidase II. Biotechnol Bioeng (2006) 93:851-61. doi:10.1002/bit.20777
110. Zhu Z, Ramakrishnan B, Li J, Wang Y, Feng Y, Prabakaran P, et al. Site-specific antibody-drug conjugation through an engineered glycotransferase and a chemically reactive sugar. MABs (2014) 6:1190-200. doi:10.4161/mabs.29889
111. Strasser R, Stadlmann J, Schahs M, Stiegler G, Quendler H, Mach L, et al. Generation of glyco-engineered Nicotiana benthamiana for the production of monoclonal antibodies with a homogeneous human-like N-glycan structure. Plant Biotechnol J (2008) 6:392-402. doi:10.1111/j.1467-7652.2008.00330.x
112. Rich JR, Withers SG. Emerging methods for the production of homogeneous human glycoproteins. Nat Chem Biol (2009) 5:206-15. doi:10.1038/nchembio.148
113. Wang LX, Lomino JV. Emerging technologies for making glycan-defined glycoproteins. ACS Chem Biol (2012) 7:110-22. doi:10.1021/cb200429n
114. Huang W, Giddens J, Fan SQ, Toonstra C, Wang LX. Chemoenzymatic glycoengineering of intact IgG antibodies for gain of functions. J Am Chem Soc (2012) 134:12308-18. doi:10.1021/ja3051266
115. Umekawa M, Huang W, Li B, Fujita K, Ashida H, Wang LX, et al. Mutants of Mucor hiemalis endo-beta-N-acetylglucosaminidase show enhanced transglycosylation and glycosynthase-like activities. J Biol Chem (2008) 283:4469-79. doi:10.1074/jbc.M707137200
116. Parsons TB, Struwe WB, Gault J, Yamamoto K, Taylor TA, Raj R, et al. Optimal synthetic glycosylation of a therapeutic antibody. Angew Chem Int Ed Engl (2016) 55:2361-7. doi:10.1002/anie.201508723
117. Huang W, Li C, Li B, Umekawa M, Yamamoto K, Zhang X, et al. Glycosynthases enable a highly efficient chemoenzymatic synthesis of N-glycoproteins carrying intact natural N-glycans. J Am Chem Soc (2009) 131:2214-23. doi:10.1021/ja8074677
118. Jung ST, Kang TH, Kelton W, Georgiou G. Bypassing glycosylation: engineering aglycosylated full-length IgG antibodies for human therapy. Curr Opin Biotechnol (2011) 22:858-67. doi:10.1016/j.copbio.2011.03.002
119. Borrok MJ, Jung ST, Kang TH, Monzingo AF, Georgiou G. Revisiting the role of glycosylation in the structure of human IgG Fc. ACS Chem Biol (2012) 7:1596-602. doi:10.1021/cb300130k
120. Ju MS, Jung ST. Aglycosylated full-length IgG antibodies: steps toward next-generation immunotherapeutics. Curr Opin Biotechnol (2014) 30:128-39. doi:10.1016/j.copbio.2014.06.013
121. Jung ST, Reddy ST, Kang TH, Borrok MJ, Sandlie I, Tucker PW, et al. Aglycosylated IgG variants expressed in bacteria that selectively bind FcgammaRI potentiate tumor cell killing by monocyte-dendritic cells. Proc Natl Acad Sci U S A (2010) 107:604-9. doi:10.1073/pnas.0908590107
122. Labrijn AF, Aalberse RC, Schuurman J. When binding is enough: nonactivating antibody formats. Curr Opin Immunol (2008) 20:479-85. doi:10.1016/j.coi.2008.05.010
123. Sazinsky SL, Ott RG, Silver NW, Tidor B, Ravetch JV, Wittrup KD. Aglycosylated immunoglobulin G1 variants productively engage activating Fc receptors. Proc Natl Acad Sci U S A (2008) 105:20167-72. doi:10.1073/pnas.0809257105
124. Jung ST, Kelton W, Kang TH, Ng DT, Andersen JT, Sandlie I, et al. Effective phagocytosis of low Her2 tumor cell lines with engineered, aglycosylated IgG displaying high FcgammaRIIa affinity and selectivity. ACS Chem Biol (2013) 8:368-75. doi:10.1021/cb300455f
125. Thomas A, Teicher BA, Hassan R. Antibody-drug conjugates for cancer therapy. Lancet Oncol (2016) 17:e254-62. doi:10.1016/S1470-2045(16)30030-4
126. Tsuchikama K, An Z. Antibody-drug conjugates: recent advances in conjugation and linker chemistries. Protein Cell (2016). doi:10.1007/s13238-016-0323-0
127. Teicher BA. Antibody drug conjugates. Curr Opin Oncol (2014) 26:476-83. doi:10.1097/CCO.0000000000000108
128. Feng Y, Zhu Z, Chen W, Prabakaran P, Lin K, Dimitrov DS. Conjugates of small molecule drugs with antibodies and other proteins. Biomedicines (2014) 2:1-13. doi:10.3390/biomedicines2010001
129. Li W, Prabakaran P, Chen W, Zhu Z, Feng Y, Dimitrov DS. Antibody aggregation: insights from sequence and structure. Antibodies (2016) 5:19. doi:10.3390/antib5030019
130. Panowski S, Bhakta S, Raab H, Polakis P, Junutula JR. Site-specific antibody drug conjugates for cancer therapy. MABs (2014) 6:34-45. doi:10.4161/mabs.27022
131. Vogel CW. Preparation of immunoconjugates using antibody oligosaccharide moieties. Methods Mol Biol (2004) 283:87-108. doi:10.1385/1-59259-813-7:087
132. Tang F, Wang L-X, Huang W. Chemoenzymatic synthesis of glycoengineered IgG antibodies and glycosite-specific antibody-drug conjugates. Nat Protoc (2017) 12:1702-21. doi:10.1038/nprot.2017.058
133. Li X, Fang T, Boons GJ. Preparation of well-defined antibody-drug conjugates through glycan remodeling and strain-promoted azide-alkyne cycloadditions. Angew Chem Int Ed Engl (2014) 53:7179-82. doi:10.1002/anie.201402606
134. van Geel R, Wijdeven MA, Heesbeen R, Verkade JMM, Wasiel AA, van Berkel SS, et al. Chemoenzymatic conjugation of toxic payloads to the globally conserved N-glycan of native mAbs provides homogeneous and highly efficacious antibody-drug conjugates. Bioconjug Chem (2015) 26:2233-42. doi:10.1021/acs.bioconjchem.5b00224
135. Seaman S, Zhu Z, Saha S, Zhang XM, Yang MY, Hilton MB, et al. Eradication of tumors through simultaneous ablation of CD276/B7-H3-positive tumor cells and tumor vasculature. Cancer Cell (2017) 31:501-515.e8. doi:10.1016/j.ccell.2017.03.005