Tailoring immunoglobulin Fc for highly potent and serum-stable therapeutic antibodies

Biotechnology and Bioprocess Engineering

Volumn 18, Issue 4, 2013, Pages 625-636

  Jung, Sang Taek ^a  

^a Kookmin University   (South Korea)

Author keywords

antibody engineering; effector functions; Fc engineering; therapeutic antibody

Indexed keywords

AMINO ACID SUBSTITUTION; ANTIBODY ENGINEERING; FC-RECEPTORS; FRONTLINE; IMMUNE EFFECTORS; INFECTIOUS PATHOGENS; SERUM STABILITY; THERAPEUTIC ANTIBODIES;

AMINO ACIDS; BODY FLUIDS;

ANTIBODIES;

COMPLEMENT; COMPLEMENT COMPONENT C1Q; FC RECEPTOR; GLYCAN; IMMUNOGLOBULIN FC FRAGMENT; MONOCLONAL ANTIBODY;

AMINO ACID SEQUENCE; ANTIBODY ENGINEERING; BINDING AFFINITY; CELLULAR IMMUNITY; DRUG EFFICACY; DRUG HALF LIFE; DRUG RECEPTOR BINDING; GLYCOSYLATION; HUMAN; HUMORAL IMMUNITY; NONHUMAN; PROCESS OPTIMIZATION; PROTEIN DOMAIN; PROTEIN EXPRESSION; PROTEIN FUNCTION; REVIEW;

EID: 84882579911     PISSN: 12268372     EISSN: 19763816     Source Type: Journal    
DOI: 10.1007/s12257-012-0711-0     Document Type: Review

References (119)

1. Montesino, R., L. Calvo, A. Vallin, P. M. Rudd, D. J. Harvey, and J. A. Cremata (2012) Structural characterization of N-linked oligosaccharides on monoclonal antibody Nimotuzumab through process development. Biologicals. 40: 288-298.
2. Tokuriki, N. and D. S. Tawfik (2009) Protein dynamism and evolvability. Sci. 324: 203-207.
3. Jung, S. T., R. Lauchli, and F. H. Arnold (2011) Cytochrome P450: Taming a wild type enzyme. Curr. Opin. Biotechnol. 22: 809-817.
4. van de Winkel, J. G. J. and P. J. A. Capel (1993) Human IgG Fc receptor heterogeneity: Molecular aspects and clinical implications. Immunol. Today 14: 215-221.
5. Berken, A. and B. Benacerraf (1966) Properties of antibodies cytophilic for macrophages. J. Exp. Med. 123: 119-144.
6. Ravetch, J. V. and S. Bolland (2001) IgG Fc receptors. Annu. Rev. Immunol. 19: 275-290.
7. Jung, S. T., T. H. Kang, W. Kelton, and G. Georgiou (2011) Bypassing glycosylation: Engineering aglycosylated full-length IgG antibodies for human therapy. Curr. Opin. Biotechnol. 22: 858-867.
8. Cohen-Solal, J. F., L. Cassard, W. H. Fridman, and C. Sautes- Fridman (2004) Fc gamma receptors. Immunol. Lett. 92: 199-205.
9. Ivan, E. and A. I. Colovai (2006) Human Fc receptors: Critical targets in the treatment of autoimmune diseases and transplant rejections. Human Immunol. 67: 479-491.
10. Bruhns, P. (2012) Properties of mouse and human IgG receptors and their contribution to disease models. Blood 119: 5640-5649.
11. Bruhns, P., B. Iannascoli, P. England, D. A. Mancardi, N. Fernandez, S. Jorieux, and M. Daëron (2009) Specificity and affinity of human Fcγ receptors and their polymorphic variants for human IgG subclasses. Blood 113: 3716-3725.
12. Jung, S. T., T. H. Kang, and G. Georgiou (2010) Efficient expression and purification of human aglycosylated Fcγ receptors in Escherichia coli. Biotechnol. Bioeng. 107: 21-30.
13. Weng, W. K. and R. Levy (2003) Two immunoglobulin G fragment C receptor polymorphisms independently predict response to rituximab in patients with follicular lymphoma. J. Clin. Oncol. 21: 3940-3947.
14. Zhang, W., M. Gordon, A. M. Schultheis, D. Y. Yang, F. Nagashima, M. Azuma, H. -M. Chang, E. Borucka, G. Lurje, A. E. Sherrod, S. Iqbal, S. Groshen, and H. -J. Lenz (2007) FCGR2A and FCGR3A polymorphisms associated with clinical outcome of epidermal growth factor receptor-expressing metastatic colorectal cancer patients treated with single-agent cetuximab. J. Clin. Oncol. 25: 3712-3718.
15. Tamura, K., C. Shimizu, T. Hojo, S. Akashi-Tanaka, T. Kinoshita, K. Yonemori, T. Kouno, N. Katsumata, M. Ando, K. Aogi, F. Koizumi, K. Nishio, and Y. Fujiwara (2011) FcγR2A and 3A polymorphisms predict clinical outcome of trastuzumab in both neoadjuvant and metastatic settings in patients with HER2-positive breast cancer. Ann. Oncol. 22: 1302-1307.
16. Yee, A. M. F., H. M. Phan, R. Zuniga, J. E. Salmon, and D. M. Musher (2000) Association between FcγRIIa-R131 allotype and bacteremic Pneumococcal pneumonia. Clin. Infect. Dis. 30: 25-28.
17. Van Sorge, N., W. Van Der Pol, and J. Van de Winkel (2003) Fc γR polymorphisms: Implications for function, disease susceptibility and immunotherapy. Tissue Antigens. 61: 189-202.
18. Sanders, L., R. G. Feldman, M. M. Voorhorst-Ogink, M. de Haas, G. T. Rijkers, P. Capel, B. Zegers, and J. Van de Winkel (1995) Human immunoglobulin G (IgG) Fc receptor IIA (CD32) polymorphism and IgG2-mediated bacterial phagocytosis by neutrophils. Infect. Immun. 63: 73-81.
19. Shashidharamurthy, R., F. Zhang, A. Amano, A. Kamat, R. Panchanathan, D. Ezekwudo, C. Zhu, and P. Selvaraj (2009) Dynamics of the interaction of human IgG subtype immune complexes with cells expressing R and H allelic forms of a lowaffinity Fcγ receptor CD32A. J. Immunol. 183: 8216-8224.
20. Karassa, F. B., T. A. Trikalinos, and J. P. A. Ioannidis (2002) Role of the Fcγ receptor IIa polymorphism in susceptibility to systemic lupus erythematosus and lupus nephritis: a meta-analysis. Arthritis Rheum. 46: 1563-1571.
21. Cartron, G., L. Dacheux, G. Salles, P. Solal-Celigny, P. Bardos, P. Colombat, and H. Watier (2002) Therapeutic activity of humanized anti-CD20 monoclonal antibody and polymorphism in IgG Fc receptor FcγRIIIa gene. Blood 99: 754-758.
22. van der Poel, C. E., R. M. Spaapen, J. G. van de Winkel, and J. H. Leusen (2011) Functional characteristics of the high affinity IgG receptor, FcγRI. J. Immunol. 186: 2699-2704.
23. Kacskovics, I. (2004) Fc receptors in livestock species. Vet. Immunol. Immunopathol. 102: 351-362.
24. Nimmerjahn, F. and J. V. Ravetch (2012) Translating basic mechanisms of IgG effector activity into next generation cancer therapies. Cancer Immun. 12: 13.
25. Rankin, C. T., M. -C. Veri, S. Gorlatov, N. Tuaillon, S. Burke, L. Huang, H. D. Inzunza, H. Li, S. Thomas, S. Johnson, J. Stavenhagen, S. Koenig, and E. Bonvini (2006) CD32B, the human inhibitory Fc-γ receptor IIB, as a target for monoclonal antibody therapy of B-cell lymphoma. Blood 108: 2384-2391.
26. Ravetch, J. V. and L. L. Lanier (2000) Immune inhibitory receptors. Sci. 290: 84-89.
27. Lu, J., J. L. Ellsworth, N. Hamacher, S. W. Oak, and P. D. Sun (2011) Crystal structure of Fcγ receptor I and its implication in high affinity γ-immunoglobulin binding. J. Biol. Chem. 286: 40608-40613.
28. Sondermann, P., J. Kaiser, and U. Jacob (2001) Molecular basis for immune complex recognition: a comparison of Fc-receptor structures. J. Mol. Biol. 309: 737-749.
29. Maxwell, K. F., M. S. Powell, M. D. Hulett, P. A. Barton, I. F. McKenzie, T. P. Garrett, and P. M. Hogarth (1999) crystal structure of the human leukocyte Fc receptor, FcγRIIa. Nat. Struct. Biol. 6: 437-442.
30. Ramsland, P. A., W. Farrugia, T. M. Bradford, C. T. Sardjono, S. Esparon, H. M. Trist, M. S. Powell, P. S. Tan, A. C. Cendron, B. D. Wines, A. M. Scott, and P. M. Hogarth (2011) Structural basis for FcγRIIa recognition of human IgG and formation of inflammatory signaling complexes. J. Immunol. 187: 3208-3217.
31. Sondermann, P. and U. Jacob (1999) Human Fcγ receptor IIb expressed in Escherichia coli reveals IgG binding capability. Biol. Chem. 380: 717-721.
32. Sondermann, P., R. Huber, V. Oosthuizen, and U. Jacob (2000) The 3.2-Å crystal structure of the human IgG1 Fc fragment-FcγRIII complex. Nature 406: 267-273.
33. Radaev, S., S. Motyka, W. H. Fridman, C. Sautes-Fridman, and P. D. Sun (2001) The structure of a human type III Fcγ receptor in complex with Fc. J. Biol. Chem. 276: 16469-16477.
34. Mizushima, T., H. Yagi, E. Takemoto, M. Shibata-Koyama, Y. Isoda, S. Iida, K. Masuda, M. Satoh, and K. Kato (2011) Structural basis for improved efficacy of therapeutic antibodies on defucosylation of their Fc glycans. Genes Cells. 16: 1071-1080.
35. Jefferis, R. (2005) Glycosylation of recombinant antibody therapeutics. Biotechnol. Prog. 21: 11-16.
36. Krapp, S., Y. Mimura, R. Jefferis, R. Huber, and P. Sondermann (2003) Structural analysis of human IgG-Fc glycoforms reveals a correlation between glycosylation and structural integrity. J. Mol. Biol. 325: 979-989.
37. Ha, S., Y. Ou, J. Vlasak, Y. Li, S. Wang, K. Vo, Y. Du, A. Mach, Y. Fang, and N. Zhang (2011) Isolation and characterization of IgG1 with asymmetrical Fc glycosylation. Glycobiol. 21: 1087-1096.
38. Feige, M. J., S. Nath, S. R. Catharino, D. Weinfurtner, S. Steinbacher, and J. Buchner (2009) Structure of the murine unglycosylated IgG1 Fc fragment. J. Mol. Biol. 391: 599-608.
39. Borrok, M. J., S. T. Jung, T. H. Kang, A. F. Monzingo, and G. Georgiou (2012) Revisiting the role of glycosylation in the structure of human IgG Fc. ACS Chem. Biol. 7: 1596-1602.
40. Shields, R. L., J. Lai, R. Keck, L. Y. O'Connell, K. Hong, Y. G. Meng, S. H. A. Weikert, and L. G. Presta (2002) Lack of fucose on human IgG1 N-linked oligosaccharide improves binding to human FcγRIII and antibody-dependent cellular toxicity. J. Biol. Chem. 277: 26733-26740.
41. Ferrara, C., S. Grau, C. Jäger, P. Sondermann, P. Brünker, I. Waldhauer, M. Hennig, A. Ruf, A. C. Rufer, M. Stihle, P. Umaña, and J. Benz (2011) Unique carbohydrate-carbohydrate interactions are required for high affinity binding between FcγRIII and antibodies lacking core fucose. Proc. Natl. Acad. Sci. USA. 108: 12669-12674.
42. Chung, S., V. Quarmby, X. Gao, Y. Ying, L. Lin, C. Reed, C. Fong, W. Lau, Z. J. Qiu, A. Shen, M. Vanderlaan, and A. Song (2012) Quantitative evaluation of fucose reducing effects in a humanized antibody on Fcγ receptor binding and antibody-dependent cell-mediated cytotoxicity activities. MAbs. 4: 326-340.
43. Kubota, T., R. Niwa, M. Satoh, S. Akinaga, K. Shitara, and N. Hanai (2009) Engineered therapeutic antibodies with improved effector functions. Cancer Sci. 100: 1566-1572.
44. Yamane-Ohnuki, N. and M. Satoh (2009) Production of therapeutic antibodies with controlled fucosylation. MAbs. 1: 230-236.
45. Malphettes, L., Y. Freyvert, J. Chang, P. -Q. Liu, E. Chan, J. C. Miller, Z. Zhou, T. Nguyen, C. Tsai, A. W. Snowden, T. N. Collingwood, P. D. Gregory, and G. J. Cost (2010) Highly efficient deletion of FUT8 in CHO cell lines using zinc-finger nucleases yields cells that produce completely nonfucosylated antibodies. Biotechnol. Bioeng. 106: 774-783.
46. Natsume, A., Y. Shimizu-Yokoyama, M. Satoh, K. Shitara, and R. Niwa (2009) Engineered anti-CD20 antibodies with enhanced complement-activating capacity mediate potent antilymphoma activity. Cancer Sci. 100: 2411-2418.
47. Shibata-Koyama, M., S. Iida, H. Misaka, K. Mori, K. Yano, K. Shitara, and M. Satoh (2009) Nonfucosylated rituximab potentiates human neutrophil phagocytosis through its high binding for FcγRIIIb and MHC class II expression on the phagocytotic neutrophils. Exp. Hematol. 37: 309-321.
48. Davies, J., L. Jiang, L. -Z. Pan, M. J. LaBarre, D. Anderson, and M. Reff (2001) Expression of GnTIII in a recombinant anti-CD20 CHO production cell line: Expression of antibodies with altered glycoforms leads to an increase in ADCC through higher affinity for FcγRIII. Biotechnol. Bioeng. 74: 288-294.
49. Umaña, P., J. Jean-Mairet, R. Moudry, H. Amstutz, and J. E. Bailey (1999) Engineered glycoforms of an antineuroblastoma IgG1 with optimized antibody-dependent cellular cytotoxic activity. Nat. Biotechnol. 17: 176-180.
50. Mossner, E., P. Brunker, S. Moser, U. Puntener, C. Schmidt, S. Herter, R. Grau, C. Gerdes, A. Nopora, E. van Puijenbroek, C. Ferrara, P. Sondermann, C. Jager, P. Strein, G. Fertig, T. Friess, C. Schull, S. Bauer, J. Dal Porto, C. Del Nagro, K. Dabbagh, M. J. Dyer, S. Poppema, C. Klein, and P. Umaña (2010) Increasing the efficacy of CD20 antibody therapy through the engineering of a new type II anti-CD20 antibody with enhanced direct and immune effector cell-mediated B-cell cytotoxicity. Blood 115: 4393-4402.
51. Anthony, R. M., F. Wermeling, and J. V. Ravetch (2012) Novel roles for the IgG Fc glycan. Ann. NY. Acad. Sci. 1253: 170-180.
52. Kaneko, Y., F. Nimmerjahn, and J. V. Ravetch (2006) Antiinflammatory activity of immunoglobulin G resulting from Fc sialylation. Sci. 313: 670-673.
53. Strasser, R., A. Castilho, J. Stadlmann, R. Kunert, H. Quendler, P. Gattinger, J. Jez, T. Rademacher, F. Altmann, L. Mach, and H. Steinkellner (2009) Improved virus neutralization by plant-produced anti-HIV antibodies with a homogeneous â1,4-galactosylated N-glycan profile. J. Biol. Chem. 284: 20479-20485.
54. Forthal, D. N., J. S. Gach, G. Landucci, J. Jez, R. Strasser, R. Kunert, and H. Steinkellner (2010) Fc-glycosylation influences Fcgamma receptor binding and cell-mediated anti-HIV activity of monoclonal antibody 2G12. J. Immunol. 185: 6876-6882.
55. Naso, M. F., S. H. Tam, B. J. Scallon, and T. S. Raju (2010) Engineering host cell lines to reduce terminal sialylation of secreted antibodies. MAbs. 2: 519-527.
56. Wang, W., S. Singh, D. L. Zeng, K. King, and S. Nema (2007) Antibody structure, instability, and formulation. J. Pharm. Sci. 96: 1-26.
57. Zou, G., H. Ochiai, W. Huang, Q. Yang, C. Li, and L. -X. Wang (2011) Chemoenzymatic synthesis and Fcγ receptor binding of homogeneous glycoforms of antibody Fc domain. presence of a bisecting sugar moiety enhances the affinity of Fc to FcγIIIa receptor. J. Am. Chem. Soc. 133: 18975-18991.
58. Presta, L. G. (2006) Engineering of therapeutic antibodies to minimize immunogenicity and optimize function. Adv. Drug Delivery Rev. 58: 640-656.
59. Armour, K. L., J. G. van de Winkel, L. M. Williamson, and M. R. Clark (2003) Differential binding to human FcγRIIa and FcγRIIb receptors by human IgG wildtype and mutant antibodies. Mol. Immunol. 40: 585-593.
60. Duncan, A. R., J. M. Woof, L. J. Partridge, D. R. Burton, and G. Winter (1988) Localization of the binding site for the human high-affinity Fc receptor on IgG. Nature 332: 563-564.
61. Lund, J., G. Winter, P. T. Jones, J. D. Pound, T. Tanaka, M. R. Walker, P. J. Artymiuk, Y. Arata, D. R. Burton, and R. Jefferis (1991) Human FcγRI and FcγRII interact with distinct but overlapping sites on human IgG. J. Immunol. 147: 2657-2662.
62. Shields, R. L., A. K. Namenuk, K. Hong, Y. G. Meng, J. Rae, J. Briggs, D. Xie, J. Lai, A. Stadlen, B. Li, J. A. Fox, and L. G. Presta (2001) High resolution mapping of the binding site on human IgG1 for FcγRI, FcγRII, FcγRIII, and FcRn and design of IgG1 variants with improved binding to the FcγR. J. Biol. Chem. 276: 6591-6604.
63. Lazar, G. A., W. Dang, S. Karki, O. Vafa, J. S. Peng, L. Hyun, C. Chan, H. S. Chung, A. Eivazi, S. C. Yoder, J. Vielmetter, D. F. Carmichael, R. J. Hayes, and B. I. Dahiyat (2006) Engineered antibody Fc variants with enhanced effector function. Proc. Natl. Acad. Sci. USA. 103: 4005-4010.
64. Richards, J. O., S. Karki, G. A. Lazar, H. Chen, W. Dang, and J. R. Desjarlais (2008) Optimization of antibody binding to FcγRIIa enhances macrophage phagocytosis of tumor cells. Mol. Cancer Ther. 7: 2517-2527.
65. Stavenhagen, J. B., S. Gorlatov, N. Tuaillon, C. T. Rankin, H. Li, S. Burke, L. Huang, S. Johnson, E. Bonvini, and S. Koenig (2007) Fc optimization of therapeutic antibodies enhances their ability to kill tumor cells in vitro and controls tumor expansion in vivo via low-affinity activating Fcγ receptors. Cancer Res. 67: 8882-8890.
66. Stavenhagen, J. B., S. Gorlatov, N. Tuaillon, C. T. Rankin, H. Li, S. Burke, L. Huang, S. Johnson, S. Koenig, and E. Bonvini (2008) Enhancing the potency of therapeutic monoclonal antibodies via Fc optimization. Adv. Enz. Regul. 48: 152-164.
67. Loo, D., R. F. Alderson, F. Z. Chen, L. Huang, W. Zhang, S. Gorlatov, S. Burke, V. Ciccarone, H. Li, Y. Yang, T. Son, Y. Chen, A. N. Easton, J. C. Li, J. R. Rillema, M. Licea, C. Fieger, T. W. Liang, J. P. Mather, S. Koenig, S. J. Stewart, S. Johnson, E. Bonvini, and P. A. Moore (2012) Development of an Fcenhanced anti-B7-H3 monoclonal antibody with potent antitumor activity. Clin. Cancer Res. 18: 3834-3845.
68. Nordstrom, J. L., S. Gorlatov, W. Zhang, Y. Yang, L. Huang, S. Burke, H. Li, V. Ciccarone, T. Zhang, and J. Stavenhagen (2011) Anti-tumor activity and toxicokinetics analysis of MGAH22, an anti-HER2 monoclonal antibody with enhanced Fcγ receptor binding properties. Breast Cancer Res. 13: R123.
69. Stewart, R., G. Thom, M. Levens, G. Güler-Gane, R. Holgate, P. M. Rudd, C. Webster, L. Jermutus, and J. Lund (2011) A variant human IgG1-Fc mediates improved ADCC. Protein Eng. Des. Sel. 24: 671-678
70. Chen, F., T. Kou, L. Fan, Z. Ye, L. Zhao, and W. -S. Tan (2011) The combined effect of sodium butyrate and low culture temperature on the production, sialylation, and biological activity of an antibody produced in CHO cells. Biotechnol. Bioproc. Eng. 16: 1157-1165.
71. Kim, T. -G., B. -G. Kim, D. -K. Jeong, Y. -S. Jang, J. -Y. Lee, and M. -S. Yang (2012) Production of monoclonal antibodies against the FimA protein of porphyromonas gingivalis in nicotiana benthamiana. Biotechnol. Bioproc. Eng. 17: 420-426.
72. Sazinsky, S. L., R. G. Ott, N. W. Silver, B. Tidor, J. V. Ravetch, and K. D. Wittrup (2008) Aglycosylated immunoglobulin G1 variants productively engage activating Fc receptors. Proc. Natl. Acad. Sci. USA. 105: 20167-20172.
73. Jung, S. T., S. T. Reddy, T. H. Kang, M. J. Borrok, I. Sandlie, P. W. Tucker, and G. Georgiou (2010) Aglycosylated IgG variants expressed in bacteria that selectively bind FcγRI potentiate tumor cell killing by monocyte-dendritic cells. Proc. Natl. Acad. Sci. USA. 107: 604-609.
74. Borrok, M. J., S. T. Jung, T. H. Kang, A. F. Monzingo, and G. Georgiou (2012) Revisiting the role of glycosylation in the structure of human IgG Fc. ACS Chem. Biol. 7: 1596-1602.
75. Tatarewicz, S. M., G. Juan, S. J. Swanson, and M. S. Moxness (2012) Epitope characterization of pre-existing and developing antibodies to an aglycosylated monoclonal antibody therapeutic of G1m17,1 allotype. J. Immunol. Methods. 382: 93-100.
76. Gaboriaud, C., J. Juanhuix, A. Gruez, M. Lacroix, C. Darnault, D. Pignol, D. Verger, J. C. Fontecilla-Camps, and G. J. Arlaud (2003) The crystal structure of the globular head of complement protein C1q provides a basis for its versatile recognition properties. J. Biol. Chem. 278: 46974-46982.
77. Arlaud, G. J., C. Gaboriaud, N. M. Thielens, and V. Rossi (2002) Structural biology of C1. Biochem. Soc. Trans. 30: 1001-1006.
78. Godau, J., T. Heller, H. Hawlisch, M. Trappe, E. Howells, J. Best, J. Zwirner, J. S. Verbeek, P. M. Hogarth, C. Gerard, N. Van Rooijen, A. Klos, J. E. Gessner, and J. Kohl (2004) C5a initiates the inflammatory cascade in immune complex peritonitis. J. Immunol. 173: 3437-3445.
79. Shushakova, N., J. Skokowa, J. Schulman, U. Baumann, J. Zwirner, R. E. Schmidt, and J. E. Gessner (2002) C5a anaphylatoxin is a major regulator of activating versus inhibitory FcγRs in immune complex-induced lung disease. J. Clin. Invest. 110: 1823-1830.
80. Kelly-Quintos, C., L. A. Cavacini, M. R. Posner, D. Goldmann, and G. B. Pier (2006) Characterization of the opsonic and protective activity against Staphylococcus aureus of fully human monoclonal antibodies specific for the bacterial surface polysaccharide poly-N-acetylglucosamine. Infect. Immun. 74: 2742-2750.
81. Wells, J., C. G. Haidaris, T. W. Wright, and F. Gigliotti (2006) Complement and Fc function are required for optimal antibody prophylaxis against Pneumocystis carinii pneumonia. Infect. Immun. 74: 390-393.
82. Racila, E., D. M. Racila, J. M. Ritchie, C. Taylor, C. Dahle, and G. J. Weiner (2006) The pattern of clinical breast cancer metastasis correlates with a single nucleotide polymorphism in the C1qA component of complement. Immunogen. 58: 1-8.
83. Tao, M. H. and S. L. Morrison (1989) 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. 143: 2595-2601.
84. Lund, J., N. Takahashi, J. D. Pound, M. Goodall, and R. Jefferis (1996) Multiple interactions of IgG with its core oligosaccharide can modulate recognition by complement and human Fcγ receptor I and influence the synthesis of its oligosaccharide chains. J. Immunol. 157: 4963-4969.
85. Dall'Acqua, W. F., K. E. Cook, M. M. Damschroder, R. M. Woods, and H. Wu (2006) Modulation of the effector functions of a human IgG1 through engineering of its hinge region. J. Immunol. 177: 1129-1138.
86. Idusogie, E. E., P. Y. Wong, L. G. Presta, H. Gazzano-Santoro, K. Totpal, M. Ultsch, and M. G. Mulkerrin (2001) Engineered antibodies with increased activity to recruit complement. J. Immunol. 166: 2571-2575.
87. Natsume, A., M. In, H. Takamura, T. Nakagawa, Y. Shimizu, K. Kitajima, M. Wakitani, S. Ohta, M. Satoh, K. Shitara, and R. Niwa (2008) Engineered antibodies of IgG1/IgG3 mixed isotype with enhanced cytotoxic activities. Cancer Res. 68: 3863-3872.
88. Idusogie, E. E., L. G. Presta, H. Gazzano-Santoro, K. Totpal, P. Y. Wong, M. Ultsch, Y. G. Meng, and M. G. Mulkerrin (2000) Mapping of the C1q binding site on rituxan, a chimeric antibody with a human IgG1 Fc. J. Immunol. 164: 4178-4184.
89. Moore, G. L., H. Chen, S. Karki, and G. A. Lazar (2010) Engineered Fc variant antibodies with enhanced ability to recruit complement and mediate effector functions. MAbs. 2: 181-189.
90. Hezareh, M., A. J. Hessell, R. C. Jensen, J. G. van de Winkel, and P. W. Parren (2001) Effector function activities of a panel of mutants of a broadly neutralizing antibody against human immunodeficiency virus type 1. J. Virol. 75: 12161-12168.
91. Dangl, J. L., T. G. Wensel, S. L. Morrison, L. Stryer, L. A. Herzenberg, and V. T. Oi (1988) Segmental flexibility and complement fixation of genetically engineered chimeric human, rabbit and mouse antibodies. Embo J. 7: 1989-1994.
92. Natsume, A., Y. Shimizu-Yokoyama, M. Satoh, K. Shitara, and R. Niwa (2009) Engineered anti-CD20 antibodies with enhanced complement-activating capacity mediate potent antilymphoma activity. Cancer Sci. 100: 2411-2418.
93. Brambell, F. W., R. Halliday, and I. G. Morris (1958) Interference by human and bovine serum and serum protein fractions with the absorption of antibodies by suckling rats and mice. Proc. R. Soc. Lond. B. Biol. Sci. 149: 1-11.
94. Jones, E. A. and T. A. Waldmann (1972) The mechanism of intestinal uptake and transcellular transport of IgG in the neonatal rat. J. Clin. Invest. 51: 2916-2927.
95. Burmeister, W. P., A. H. Huber, and P. J. Bjorkman (1994) Crystal structure of the complex of rat neonatal Fc receptor with Fc. Nature 372: 379-383.
96. Martin, W. L., A. P. West, L. Gan, and P. J. Bjorkman (2001) Crystal structure at 2.8Å of an FcRn/heterodimeric Fc complex: Mechanism of pH-dependent binding. Mol. Cell. 7: 867-877.
97. West, A. P. and P. J. Bjorkman (2000) Crystal structure and immunoglobulin G binding properties of the human major histocompatibility complex-related Fc receptor. Biochem. 39: 9698-9708.
98. Raghavan, M. and P. J. Bjorkman (1996) Fc receptors and their interactions with immunoglobulins. Annu. Rev. Cell Dev. Biol. 12: 181-220.
99. Ober, R. J., C. Martinez, X. Lai, J. Zhou, and E. S. Ward (2004) Exocytosis of IgG as mediated by the receptor, FcRn: An analysis at the single-molecule level. Proc. Natl. Acad. Sci. USA. 101: 11076-11081.
100. Ober, R. J., C. Martinez, C. Vaccaro, J. Zhou, and E. S. Ward (2004) Visualizing the site and dynamics of IgG salvage by the MHC Class I-related receptor, FcRn. J. Immunol. 172: 2021-2029.
101. Rodewald, R. (1976) pH-dependent binding of immunoglobulins to intestinal cells of the neonatal rat. J. Cell Biol. 71: 666-669.
102. Ghetie, V. and E. S. Ward (2000) Multiple roles for the major histocompatibility complex class I-related receptor FcRn. Annu. Rev. Immunol. 18: 739-766.
103. Baker, K., S. -W. Qiao, T. T. Kuo, V. G. Aveson, B. Platzer, J. -T. Andersen, I. Sandlie, Z. Chen, C. de Haar, W. I. Lencer, E. Fiebiger, and R. S. Blumberg (2011) Neonatal Fc receptor for IgG (FcRn) regulates cross-presentation of IgG immune complexes by CD8-CD11b+ dendritic cells. Proc. Natl. Acad. Sci. 108: 9927-9932.
104. Vidarsson, G., A. M. Stemerding, N. M. Stapleton, S. E. Spliethoff, H. Janssen, F. E. Rebers, M. de Haas, and J. G. van de Winkel (2006) FcRn: An IgG receptor on phagocytes with a novel role in phagocytosis. Blood 108: 3573-3579.
105. Dall'Acqua, W. F., R. M. Woods, E. S. Ward, S. R. Palaszynski, N. K. Patel, Y. A. Brewah, H. Wu, P. A. Kiener, and S. Langermann (2002) Increasing the affinity of a human IgG1 for the neonatal Fc receptor: Biological consequences. J. Immunol. 169: 5171-5180.
106. Dall'Acqua, W. F., P. A. Kiener, and H. Wu (2006) Properties of human IgG1s engineered for enhanced binding to the neonatal Fc receptor (FcRn). J. Biol. Chem. 281: 23514-23524.
107. Ghetie, V., S. Popov, J. Borvak, C. Radu, D. Matesoi, C. Medesan, R. J. Ober, and E. S. Ward (1997) Increasing the serum persistence of an IgG fragment by random mutagenesis. Nat. Biotechnol. 15: 637-640.
108. Hinton, P. R., J. M. Xiong, M. G. Johlfs, M. T. Tang, S. Keller, and N. Tsurushita (2006) An engineered human IgG1 antibody with longer serum half-life. J. Immunol. 176: 346-356.
109. Yeung, Y. A., M. K. Leabman, J. S. Marvin, J. Qiu, C. W. Adams, S. Lien, M. A. Starovasnik, and H. B. Lowman (2009) Engineering human IgG1 affinity to human neonatal Fc receptor: Impact of affinity improvement on pharmacokinetics in primates. J. Immunol. 182: 7663-7671.
110. Zalevsky, J., A. K. Chamberlain, H. M. Horton, S. Karki, I. W. L. Leung, T. J. Sproule, G. A. Lazar, D. C. Roopenian, and J. R. Desjarlais (2010) Enhanced antibody half-life improves in vivo activity. Nat. Biotechnol. 28: 157-159.
111. Kim, J. K., M. F. Tsen, V. Ghetie, and E. S. Ward (1994) Localization of the site of the murine IgG1 molecule that is involved in binding to the murine intestinal Fc receptor. Eur. J. Immunol. 24: 2429-2434.
112. Medesan, C., P. Cianga, M. Mummert, D. Stanescu, V. Ghetie, and E. S. Ward (1998) Comparative studies of rat IgG to further delineate the Fc: FcRn interaction site. Eur. J. Immunol. 28: 2092-2100.
113. Weng, Z., K. Gulukota, D. E. Vaughn, P. J. Bjorkman, and C. DeLisi (1998) Computational determination of the structure of rat Fc bound to the neonatal Fc receptor. J. Mol. Biol. 282: 217-225.
114. Oganesyan, V., M. M. Damschroder, R. M. Woods, K. E. Cook, H. Wu, and W. F. Dall'Acqua (2009) Structural characterization of a human Fc fragment engineered for extended serum halflife. Mol. Immunol. 46: 1750-1755.
115. Stapleton, N. M., J. T. Andersen, A. M. Stemerding, S. P. Bjarnarson, R. C. Verheul, J. Gerritsen, Y. Zhao, M. Kleijer, I. Sandlie, M. de Haas, I. Jonsdottir, C. E. van der Schoot, and G. Vidarsson (2011) Competition for FcRn-mediated transport gives rise to short half-life of human IgG3 and offers therapeutic potential. Nat. Commun. 2: 599.
116. Jung, S. T., W. Kelton, T. H. Kang, D. Ng, J. T. Andersen, I. Sandlie, C. Sarkar, and G. Georgiou (2012) Effective phagocytosis of low Her2 tumor cell lines with engineered, aglycosylated IgG displaying high FcγRIIa affinity and selectivity. ACS Chem. Biol. 8: 368-375.
117. Veri, M. C., S. Gorlatov, H. Li, S. Burke, S. Johnson, J. Stavenhagen, K. E. Stein, E. Bonvini, and S. Koenig (2007) Monoclonal antibodies capable of discriminating the human inhibitory Fcgamma-receptor IIB (CD32B) from the activating Fcgamma-receptor IIA (CD32A): Biochemical, biological and functional characterization. Immunol. 121: 392-404.
118. Roopenian, D. C., G. J. Christianson, and T. J. Sproule (2010) Human FcRn transgenic mice for pharmacokinetic evaluation of therapeutic antibodies. Methods Mol. Biol. 602: 93-104.
119. Smith, P., D. J. DiLillo, S. Bournazos, F. Li, and J. V. Ravetch (2012) Mouse model recapitulating human Fcγ receptor structural and functional diversity. Proc. Natl. Acad. Sci. USA. 109: 6181-6186.