Engineering upper hinge improves stability and effector function of a human IgG1

Journal of Biological Chemistry

Volumn 287, Issue 8, 2012, Pages 5891-5897

  Yan, Boxu ^a   Boyd, Daniel ^a   Kaschak, Timothy ^a   Tsukuda, Joni ^a   Shen, Amy ^a   Lin, Yuwen ^a   Chung, Shan ^a   Gupta, Priyanka ^a   Kamath, Amrita ^a   Wong, Anne ^a   Vernes, Jean Michel ^a   Meng, Gloria Y ^a   Totpal, Klara ^a   Schaefer, Gabriele ^a   Jiang, Guoying ^a   Nogal, Bartek ^a   Emery, Craig ^a   Vanderlaan, Martin ^a   Carter, Paul ^a   Harris, Reed ^a   Amanullah, Ashraf ^a   more..

^a GENENTECH INC   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ANTIBODY ENGINEERING; ELECTRON TRANSFER; INDUCED DEGRADATION; PHARMACOKINETIC PROFILES; RADICAL ATTACKS; RADICAL REACTIONS; REDOX POTENTIALS; REDOX-ACTIVE; WILD TYPES;

ANTIBODIES; DEGRADATION; REACTION KINETICS; REDOX REACTIONS;

FREE RADICAL REACTIONS;

ASPARTIC ACID; CD16 ANTIGEN; CYSTEINE; HISTIDINE; IMMUNOGLOBULIN G1; TYROSINE;

AMINO ACID SUBSTITUTION; ANTIBODY COMBINING SITE; ANTIBODY DEPENDENT CELLULAR CYTOTOXICITY; ANTIBODY ENGINEERING; ANTIGEN BINDING; ARTICLE; CONTROLLED STUDY; HEAVY CHAIN; HINGE REGION; LIGHT CHAIN; MUTANT; OXIDATION REDUCTION POTENTIAL; PRIORITY JOURNAL; PROTEIN CLEAVAGE; PROTEIN DEGRADATION; PROTEIN FUNCTION; PROTEIN STABILITY; UPPER HINGE;

AMINO ACID SEQUENCE; AMINO ACID SUBSTITUTION; ANIMALS; CHO CELLS; CRICETINAE; CRICETULUS; FEASIBILITY STUDIES; HUMANS; HYDROXYL RADICAL; IMMUNOGLOBULIN G; IMMUNOGLOBULIN HEAVY CHAINS; IMMUNOGLOBULIN LIGHT CHAINS; MOLECULAR SEQUENCE DATA; MUTATION; PROTEIN ENGINEERING; PROTEIN STABILITY; PROTEOLYSIS;

EID: 84863175304     PISSN: 00219258     EISSN: 1083351X     Source Type: Journal    
DOI: 10.1074/jbc.M111.311811     Document Type: Article

References (35)

1. Nelson, A. L., Dhimolea, E., and Reichert, J. M. (2010) Development trends for human monoclonal antibody therapeutics. Nat. Rev. Drug Discov. 9, 767-774
2. Carter, P. J. (2006) Potent antibody therapeutics by design. Nat. Rev. Immunol. 6, 343-357
3. Nelson, A. L., and Reichert, J. M. (2009) Development trends for therapeutic antibody fragments. Nat. Biotechnol. 27, 331-337
4. Beck, A., Wurch, T., Bailly, C., and Corvaia, N. (2010) Strategies and challenges for the next generation of therapeutic antibodies. Nat. Rev. Immunol. 10, 345-352
5. Jefferis, R. (2009) Glycosylation as a strategy to improve antibody-based therapeutics. Nat. Rev. Drug Discov. 8, 226-234
6. Walsh, G., and Jefferis, R. (2006) Post-translational modifications in the context of therapeutic proteins. Nat. Biotechnol. 24, 1241-1252
7. Schneider, C. K., and Kalinke, U. (2008) Toward biosimilar monoclonal antibodies. Nat. Biotechnol. 26, 985-990
8. Reichert, J. M., and Valge-Archer, V. E. (2007) Development trends for monoclonal antibody cancer therapeutics. Nat. Rev. Drug Discov. 6, 349-356
9. Yan, B., Yates, Z., Balland, A., and Kleemann, G. R. (2009) Human IgG1 hinge fragmentation as the result of H2O2-mediated radical cleavage. J. Biol. Chem. 284, 35390-35402
10. Yates, Z., Gunasekaran, K., Zhou, H., Hu, Z., Liu, Z., Ketchem, R. R., and Yan, B. (2010) Histidine residue mediates radical-induced hinge cleavage of human IgG1. J. Biol. Chem. 285, 18662-18671
11. Yan, B., and Boyd, D. (2011) Breaking the light and heavy chain linkage of human immunoglobulin G1 (IgG1) by radical reactions. J. Biol. Chem. 286, 24674-24684
12. Garrison, W. M. (1987) Reaction mechanisms in the radiolysis of peptides, polypeptides, and proteins. Chem. Rev 87, 381-388
13. Reece, S. Y., and Nocera, D. G. (2009) Proton-coupled electron transfer in biology: results from synergistic studies in natural and model systems. Annu. Rev. Biochem. 78, 673-699
14. Davies, M. J., and Dean, R. T (1997) Radical-mediated Protein Oxidation pp. 50-120, Oxford University Press, Oxford, U.K.
15. Dall'Acqua, W. F., Cook, K. E., Damschroder, M. M., Woods, R. M., and Wu, H. (2006) Modulation of the effector functions of a human IgG1 through engineering of its hinge region. J. Immunol. 177, 1129-1138
16. Lu, Y., Vernes, J. M., Chiang, N., Ou, Q., Ding, J., Adams, C., Hong, K., Truong, B. T., Ng, D., Shen, A., Nakamura, G., Gong, Q., Presta, L. G., Beresini, M., Kelley, B., Lowman, H., Wong, W. L., and Meng, Y. G. (2011) Identification of IgG(1) variants with increased affinity to FcγRIIIa and unaltered affinity to FcγRI and FcRn: comparison of soluble receptor-based and cell-based binding assays. J. Immunol. Methods 365, 132-141
17. Shields, R. L., Namenuk, A. K., Hong, K., Meng, Y. G., Rae, J., Briggs, J., Xie, D., Lai, J., Stadlen, A., Li, B., Fox, J. A., and Presta, L. G. (2001) High resolution mapping of the binding site on human IgG1 for Fcγ RI, Fcγ RII, Fc γ RIII, and FcRn and design of IgG1 variants with improved binding to the Fc γ R. J. Biol. Chem. 276, 6591-6604
18. Saphire, E. O., Stanfield, R. L., Crispin, M. D., Parren, P. W., Rudd, P. M., Dwek, R. A., Burton, D. R., and Wilson, I. A. (2002) Contrasting IgG structures reveal extreme asymmetry and flexibility. J. Mol. Biol. 319, 9-18
19. Stewart, R., Thom, G., Levens, M., Güler-Gane, G., Holgate, R., Rudd, P. M., Webster, C., Jermutus, L., and Lund, J. (2011) A variant human IgG1-Fc mediates improved ADCC. Protein Eng. Des. Sel. 24, 671-678
20. Kirby, J. P., and Nocera, D. G. (1997) Significant effect of salt bridges on electron transfer. J. Am. Chem. Soc. 119, 9230-9236
21. Mohammad, R., Seyedsayamdost, J. X., Clement, T. Y., Chan, P. G., and Schultz, J. S. (2007) Site-specific insertion of 3-aminotyrosine into subunit α2 of E. coli ribonucleotide reductase: direct evidence for involvement of Y730 and Y731 in radical propagation. J. Am. Chem. Soc. 129, 15060-15071
22. Seyedsayamdost, M. R., Yee, C. S., Reece, S. Y., Nocera, D. G., and Stubbe, J. (2006) pH rate profiles of FnY356-R2s (n = 2, 3, 4) in Escherichia coli ribonucleotide reductase: evidence that Y356 is a redox-active amino acid along the radical propagation pathway. J. Am. Chem. Soc. 128, 1562-1568
23. Chan, A. C., and Carter, P. J. (2010) Therapeutic antibodies for autoimmunity and inflammation. Nat. Rev. Immunol. 10, 301-316
24. Jiang, X. R., Song, A., Bergelson, S., Arroll, T., Parekh, B., May, K., Chung, S., Strouse, R., Mire-Sluis, A., and Schenerman, M. (2011) Advances in the assessment and control of the effector functions of therapeutic antibodies. Nat. Rev. Drug Discov. 10, 101-111
25. Lazar, G. A., Dang, W., Karki, S., Vafa, O., Peng, J. S., Hyun, L., Chan, C., Chung, H. S., Eivazi, A., Yoder, S. C., Vielmetter, J., Carmichael, D. F., Hayes, R. J., and Dahiyat, B. I. (2006) Engineered antibody Fc variants with enhanced effector function. Proc. Natl. Acad. Sci. U.S.A. 103, 4005-4010
26. Page, C. C., Moser, C. C., and Dutton, P. L. (2003) Mechanism for electron transfer within and between proteins. Curr. Opin Chem. Biol. 7, 551-556
27. Page, C. C., Moser, C. C., Chen, X., and Dutton, P. L. (1999) Natural engineering principles of electron tunneling in biological oxidation-reduction. Nature 402, 47-52
28. Horne, C., Klein, M., Polodoulis, I., and Dorrkingtin, K. J. (1982) Noncovalent association of heavy and light chains of human immunoglobulins. III. Specific interactions between VH and VL. J. Immunol. 129, 660-664
29. Goldmacher, V. S., and Kovtun, Y. V. (2011) Antibody-drug conjugates: using monoclonal antibodies for delivery of cytotoxic payloads to cancer cells. Therapeutic Delivery 2, 397-416
30. Ducry, L., and Stump, B. (2010) Antibody-Drug Conjugates: Linking Cytotoxic Payloads to Monoclonal Antibodies. Bioconjugate Chem. 21, 5-13
31. Datta-Mannan, A., Witcher, D. R., Tang, Y., Watkins, J., and Wroblewski, V. J. (2007) Monoclonal antibody clearance. Impact of modulating the interaction of IgG with the neonatal Fc receptor. J. Biol. Chem. 282, 1709-1717
32. Yeung, Y. A. Leabman, M. K., Marvin, J. S., Qiu, J., Adams, C. W., Lien, S. Starovasnik, M. A. and Lowman, H. B. (2009) Engineering human IgG1 affinity to human neonatal Fc receptor: impact of affinity improvement on pharmacokinetics in primates. J. Immunol. 182, 7663-7671
33. Roopenian, D. C., and Akilesh, S. (2007) FcRn: the neonatal Fc receptor comes of age. Nat. Rev. Immunol. 7, 715-725
34. Tabrizi, M. A., Tseng, C. M., and Roskos, L. K. (2006) Elimination mechanisms of therapeutic monoclonal antibodies. Drug Discov. Today 11, 81-88
35. Oganesyan, V., Damschroder, M. M., Leach, W., Wu, H., and Dall'Acqua, W. F. (2008) Structural characterization of a mutated, ADCC-enhanced human Fc fragment. Mol. Immunol. 45, 1872-1882