Cited by 357Monoclonal and Polyclonal Antibodies ResearchProtein purification and stabilityImmune Cell Function and Interaction

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IgG Fc engineering to modulate antibody effector functions

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Wang, Xinhua, Mathieu, Mary, Brezski, Randall J.·2018·Protein & Cell

DOI 10.1007/s13238-017-0473-8PMC PMC5777978

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Abstract

Therapeutic monoclonal antibodies are among the most effective biotherapeutics to date. An important aspect of antibodies is their ability to bind antigen while at the same time recruit immune effector functions. The majority of approved recombinant monoclonal antibody therapies are of the human IgG1 subclass, which can engage both humoral and cellular components of the immune system. The wealth of information generated about antibodies has afforded investigators the ability to molecularly engineer antibodies to modulate effector functions. Here, we review various antibody engineering efforts intended to improve efficacy and safety relative to the human IgG isotype. Further, we will discuss proposed mechanisms by which engineering approaches led to modified interactions with immune components and provide examples of clinical studies using next generation antibodies.

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Figure 1 The Fc domain of human IgG1 is shown (PDBID:3AVE). The positions of amino acids described in Table 1 are shown. Key sequence motifs for FcRn interactions are shown in green (L251-S254; L309-Q311; N434-H435) (Oganesyan et al., 2014). Amino acids 5 angstroms proximal to the FcγR:Fc interface for FcγRI (PDBID:4W4O) (Kiyoshi et al., 2015), FcγRIIa (PDBID:3RY6) (Ramsland et al., 2011), FcγRIIb (PDBID:3WJJ) (Mimoto et al., 2013b), and FcγRIIIb (PDBID:1E4K) (Sondermann et al., 2000) as determined with PyMOL are shown in red (P232-S239; D265-D270; Y296-T299; N325-I332). The amino acids that are critical for interactions with C1q are shown in blue (D270, K322, P329, P331) (Idusogie et al., 2000). Amino acids depicted in black were not identified as critical for interactions with FγRs, FcRn, or C1q. Figure 1 was generated with PyMOL.CC BY · PubMed Central

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Fcγ receptors as regulators of immune responses
Nimmerjahn, F., & Ravetch, J. V. (2008) · Nature Reviews Immunology · doi:10.1038/nri2206 · Cited by 2,947
FcRn: the neonatal Fc receptor comes of age
Roopenian, D. C., & Akilesh, S. (2007) · Nature Reviews Immunology · doi:10.1038/nri2155 · Cited by 2,346
Therapeutic activity of humanized anti-CD20 monoclonal antibody and polymorphism in IgG Fc receptor FcγRIIIa gene
Cartron, G., Dacheux, L., Salles, G. A., Solal‐Céligny, P., BARDOS, P., Colombat, P., & Watier, H. (2002) · Blood · doi:10.1182/blood.v99.3.754 · Cited by 1,954
Lack of Fucose on Human IgG1 N-Linked Oligosaccharide Improves Binding to Human FcγRIII and Antibody-dependent Cellular Toxicity
Shields, R. L., Lai, J., Keck, R., O'Connell, L. Y., Hong, K., Meng, Y. G., Weikert, S. H. A., & Presta, L. G. (2002) · Journal of Biological Chemistry · doi:10.1074/jbc.m202069200 · Cited by 1,835
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
Shinkawa, T., Nakamura, K., Yamane, N., Shoji-Hosaka, E., Kanda, Y., Sakurada, M., Uchida, K., Anazawa, H., Satoh, M., Yamasaki, M., et al. (2003) · Journal of Biological Chemistry · doi:10.1074/jbc.m210665200 · Cited by 1,413
The therapeutic monoclonal antibody market
Ecker, D. M., Jones, S. D., & Levine, H. L. (2014) · mAbs · doi:10.4161/19420862.2015.989042 · Cited by 1,369
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
Shields, R. L., Namenuk, A. K., Hong, K., Meng, Y. G., Rae, J., Briggs, J. B., Xie, D., Lai, J., Stadlen, A., Li, B., et al. (2001) · Journal of Biological Chemistry · doi:10.1074/jbc.m009483200 · Cited by 1,172
Potent antibody therapeutics by design
Carter, P. J. (2006) · Nature reviews. Immunology · doi:10.1038/nri1837 · Cited by 1,124
THE COVALENT STRUCTURE OF AN ENTIRE γG IMMUNOGLOBULIN MOLECULE
Edelman, G. M., Cunningham, B. A., Gall, W. E., Gottlieb, P. D., Rutishauser, U. S., & Waxdal, M. J. (1969) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.63.1.78 · Cited by 903
Engineered antibody Fc variants with enhanced effector function
Lazar, G. A., Dang, W., Karki, S., Vafa, O., Peng, J. S., Hyun, L., Chan, C. S. C., Chung, H. S., Eivazi, A., Yoder, S. C., et al. (2006) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0508123103 · Cited by 824
Complement Is Activated by IgG Hexamers Assembled at the Cell Surface
Diebolder, C. A., Beurskens, F. J. M., de Jong, R. N., Koning, R. I., Strumane, K., Lindorfer, M. A., Voorhorst, M., Ugurlar, D., Rosati, S., Heck, A. J. R., et al. (2014) · Science · doi:10.1126/science.1248943 · Cited by 797
Discovery and Development of the Complement Inhibitor Eculizumab for the Treatment of Paroxysmal Nocturnal Hemoglobinuria
Rother, R. P., Rollins, S. A., Mojcik, C. F., Brodsky, R. A., & Bell, L. (2007) · Nature Biotechnology · doi:10.1038/nbt1344 · Cited by 778 · cited 3×
“The approved anti-C5 therapeutic, eculizumab, has the IgG2 amino acids 118 to 260 and the IgG4 amino acids 261 to 447 and has been shown to have limited or undetectable effector function (Rother et al., 2007).”
Background
Unique carbohydrate-carbohydrate interactions are required for high affinity binding between FcγRIII and antibodies lacking core fucose
Ferrara, C., Grau, S., Jäger, C., Sondermann, P., Brünker, P., Waldhauer, I., Hennig, M., Ruf, A., Rufer, A. C., Stihle, M., et al. (2011) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1108455108 · Cited by 770
Engineered glycoforms of an antineuroblastoma IgG1 with optimized antibody-dependent cellular cytotoxic activity
Umaña, P., Jean–Mairet, J., Moudry, R., Amstutz, H., & Bailey, J. E. (1999) · Nature Biotechnology · doi:10.1038/6179 · Cited by 764
The 3.2-Å crystal structure of the human IgG1 Fc fragment–FcγRIII complex
Sondermann, P., Huber, R., Oosthuizen, V., & Jacob, U. (2000) · Nature · doi:10.1038/35018508 · Cited by 735
The protection receptor for IgG catabolism is the beta2-microglobulin-containing neonatal intestinal transport receptor.
Junghans, R. P., & Anderson, C. L. (1996) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.93.11.5512 · Cited by 696
Enhanced antibody half-life improves in vivo activity
Zalevsky, J., Chamberlain, A. K., Horton, H. M., Karki, S., Leung, I., Sproule, T. J., Lazar, G. A., Roopenian, D. C., & Desjarlais, J. R. (2010) · Nature Biotechnology · doi:10.1038/nbt.1601 · Cited by 667
Properties of Human IgG1s Engineered for Enhanced Binding to the Neonatal Fc Receptor (FcRn)
Dall’Acqua, W. F., Kiener, P. A., & Wu, H. (2006) · Journal of Biological Chemistry · doi:10.1074/jbc.m604292200 · Cited by 648
The Biological Activity of Human CD20 Monoclonal Antibodies Is Linked to Unique Epitopes on CD20
Teeling, J. L., Mackus, W. J. M., Wiegman, L., van den Brakel, J. H. N., Beers, S. A., French, R. R., van Meerten, T., Ebeling, S. B., Vink, T., Slootstra, J. W., et al. (2006) · The Journal of Immunology · doi:10.4049/jimmunol.177.1.362 · Cited by 609
Studies of aglycosylated chimeric mouse-human IgG. Role of carbohydrate in the structure and effector functions mediated by the human IgG constant region.
Tao, M., & Morrison, S. L. (1989) · The Journal of Immunology · doi:10.4049/jimmunol.143.8.2595 · Cited by 531
Metabolic properties of IgG subclasses in man
Morell, A., Terry, W. D., & Waldmann, T. A. (1970) · Journal of Clinical Investigation · doi:10.1172/jci106279 · Cited by 523
Impact of FcγRIIa-FcγRIIIa Polymorphisms and KRAS Mutations on the Clinical Outcome of Patients With Metastatic Colorectal Cancer Treated With Cetuximab Plus Irinotecan
Bibeau, F., Lopez-Crapez, E., Di Fiore, F., Thezenas, S., Ychou, M., Blanchard, F., Lamy, A., Penault-Llorca, F., Frébourg, T., Michel, P., et al. (2009) · Journal of Clinical Oncology · doi:10.1200/jco.2008.18.0463 · Cited by 521
Disulfide bond structures of IgG molecules
Liu, H., & May, K. M. L. (2012) · mAbs · doi:10.4161/mabs.4.1.18347 · Cited by 487
Abnormally short serum half‐lives of IgG in β2‐microglobulin‐deficient mice
Ghetie, V. F., Hubbard, J. G., Kim, J., Tsen, M. F., Lee, Y., & Ward, E. S. (1996) · European Journal of Immunology · doi:10.1002/eji.1830260327 · Cited by 478
THE TRANSMISSION OF IMMUNITY FROM MOTHER TO YOUNG AND THE CATABOLISM OF IMMUNOGLOBULINS
Brambell, F. W. R. (1966) · The Lancet · doi:10.1016/s0140-6736(66)92190-8 · Cited by 471
A Theoretical Model of γ-Globulin Catabolism
Brambell, F. W. R., Hemmings, W. A., & MORRIS, I. G. (1964) · Nature · doi:10.1038/2031352a0 · Cited by 461
Crystal structure of the complex of rat neonatal Fc receptor with Fc
Burmeister, W. P., Huber, A. H., & Björkman, P. J. (1994) · Nature · doi:10.1038/372379a0 · Cited by 442
Mapping of the C1q Binding Site on Rituxan, a Chimeric Antibody with a Human IgG1 Fc
Idusogie, E. E., Presta, L. G., Gazzano, H., Tótpál, K., Wong, P. Y., Ultsch, M. H., Meng, Y. G., & Mulkerrin, M. G. (2000) · The Journal of Immunology · doi:10.4049/jimmunol.164.8.4178 · Cited by 424
CD3-specific antibodies: a portal to the treatment of autoimmunity
Chatenoud, L., & Bluestone, J. A. (2007) · Nature reviews. Immunology · doi:10.1038/nri2134 · Cited by 401
Crystal Structure at 2.8 Å of an FcRn/Heterodimeric Fc Complex
Martin, W. L., West, A. P., Gan, L., & Bjorkman, P. J. (2001) · Molecular Cell · doi:10.1016/s1097-2765(01)00230-1 · Cited by 391
Crystal structure of the complex of rat neonatal Fc receptor with Fc
(1995) · Trends in Genetics · doi:10.1016/0168-9525(95)90005-5 · Cited by 382
Increasing the Affinity of a Human IgG1 for the Neonatal Fc Receptor: Biological Consequences
Acqua, W. F. D., Woods, R. M., Ward, E. S., Palaszynski, S., Patel, N., Brewah, Y. A., Wu, H., Kiener, P. A., & Langermann, S. (2002) · The Journal of Immunology · doi:10.4049/jimmunol.169.9.5171 · Cited by 372
The Immunoglobulin FactsBook
Lefranc, M., & Lefranc, M. (2001) · Cited by 367
A Novel Investigational Fc-Modified Humanized Monoclonal Antibody, Motavizumab-YTE, Has an Extended Half-Life in Healthy Adults
Robbie, G. J., Criste, R., Dall'Acqua, W. F., Jensen, K., Patel, N. K., Losonsky, G. A., & Griffin, M. P. (2013) · Antimicrobial Agents and Chemotherapy · doi:10.1128/aac.01285-13 · Cited by 366
The Structure of a Human Type III Fcγ Receptor in Complex with Fc
Radaev, S., Motyka, S. A., Fridman, W. H., Sautès‐Fridman, C., & Sun, P. D. (2001) · Journal of Biological Chemistry · doi:10.1074/jbc.m100350200 · Cited by 358
Crystal structure at 2.2 Å resolution of the MHC-related neonatal Fc receptor
Burmeister, W. P., Gastinel, L. N., Simister, N. E., Blum, M. L., & Björkman, P. J. (1994) · Nature · doi:10.1038/372336a0 · Cited by 336
Increased clearance of IgG in mice that lack β2‐microglobulin: possible protective role of FcRn
Israel, E. J., Wilsker, D. F., Hayes, K. C., Schoenfeld, D., & Simister, N. E. (1996) · Immunology · doi:10.1046/j.1365-2567.1996.d01-775.x · Cited by 334
Optimization of antibody binding to FcγRIIa enhances macrophage phagocytosis of tumor cells
Richards, J. O., Karki, S., Lazar, G. A., Chen, H., Dang, W., & Desjarlais, J. R. (2008) · Molecular Cancer Therapeutics · doi:10.1158/1535-7163.mct-08-0201 · Cited by 328
Effector-attenuating Substitutions That Maintain Antibody Stability and Reduce Toxicity in Mice
Lo, M., Kim, H. S., Tong, R. K., Bainbridge, T. W., Vernes, J.-M., Zhang, Y., Lin, Y. L., Chung, S., Dennis, M. S., Zuchero, Y. J. Y., et al. (2017) · Journal of Biological Chemistry · doi:10.1074/jbc.m116.767749 · Cited by 317
Self-citation
Current progress in innovative engineered antibodies
Strohl, W. R. (2017) · Protein & Cell · doi:10.1007/s13238-017-0457-8 · Cited by 296
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
Stavenhagen, J. B., Gorlatov, S. N., Tuaillon, N., Rankin, C. T., Li, H., Burke, S., Huang, L., Johnson, S., Bonvini, E., & Koenig, S. (2007) · Cancer Research · doi:10.1158/0008-5472.can-07-0696 · Cited by 292
Engineered Antibodies with Increased Activity to Recruit Complement
Idusogie, E. E., Wong, P. Y., Presta, L. G., Gazzano, H., Tótpál, K., Ultsch, M. H., & Mulkerrin, M. G. (2001) · The Journal of Immunology · doi:10.4049/jimmunol.166.4.2571 · Cited by 291
Localization of the binding site for the human high-affinity Fc receptor on IgG
Duncan, A., Woof, J. M., Partridge, L. J., Burton, D. R., & Winter, G. P. (1988) · Nature · doi:10.1038/332563a0 · Cited by 288
Engineered Fc variant antibodies with enhanced ability to recruit complement and mediate effector functions
Moore, G. L., Chen, H., Karki, S., & Lazar, G. A. (2010) · mAbs · doi:10.4161/mabs.2.2.11158 · Cited by 266
The binding affinity of human IgG for its high affinity Fc receptor is determined by multiple amino acids in the CH2 domain and is modulated by the hinge region.
Canfield, S. M., & Morrison, S. L. (1991) · The Journal of Experimental Medicine · doi:10.1084/jem.173.6.1483 · Cited by 266
Structural Insights into Neonatal Fc Receptor-based Recycling Mechanisms
Oganesyan, V., Damschroder, M. M., Cook, K. E., Li, Q., Gao, C., Wu, H., & Dall'Acqua, W. F. (2014) · Journal of Biological Chemistry · doi:10.1074/jbc.m113.537563 · Cited by 259
Molecular engineering and design of therapeutic antibodies
Presta, L. G. (2008) · Current Opinion in Immunology · doi:10.1016/j.coi.2008.06.012 · Cited by 256
Structural features of human immunoglobulin G that determine isotype-specific differences in complement activation.
Tao, M., Smith, R. I., & Morrison, S. L. (1993) · The Journal of Experimental Medicine · doi:10.1084/jem.178.2.661 · Cited by 251
Antibodies to watch in 2017
Reichert, J. M. (2016) · mAbs · doi:10.1080/19420862.2016.1269580 · Cited by 250
In Vitro Characterization of Five Humanized OKT3 Effector Function Variant Antibodies
Xu, D., Alegre, M., Varga, S. S., Rothermel, A. L., Collins, A., Pulito, V. L., Hanna, L. S., Dolan, K. P., Parren, P. W. H. I., Bluestone, J. A., et al. (2000) · Cellular Immunology · doi:10.1006/cimm.2000.1617 · Cited by 240
First-in-human phase 1 study of margetuximab (MGAH22), an Fc-modified chimeric monoclonal antibody, in patients with HER2-positive advanced solid tumors
Bang, Y., Giaccone, G., Im, S.-A., Oh, D., Bauer, T. M., Nordstrom, J. L., Li, H., Chichili, G. R., Moore, P. A., Hong, S.-H., et al. (2017) · Annals of Oncology · doi:10.1093/annonc/mdx002 · Cited by 229
Potential Mechanisms for Thrombocytopenia Development with Trastuzumab Emtansine (T-DM1)
Uppal, H., Doudement, E., Mahapatra, K., Darbonne, W. C., Bumbaca, D., Shen, B., Du, X., Saad, O. M., Bowles, K. H., Olsen, S., et al. (2014) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-14-2093 · Cited by 220
The generation of a humanized, non‐mitogenic CD3 monoclonal antibody which retains in vitro immunosuppressive properties
Bolt, S. L., Routledge, E. G., LLOYD, I. S., Chatenoud, L., Pope, H., Gorman, S. D., Clark, M., & Waldmann, H. (1993) · European Journal of Immunology · doi:10.1002/eji.1830230216 · Cited by 217
Human Fc gamma RI and Fc gamma RII interact with distinct but overlapping sites on human IgG
Lund, J., Winter, G., Jones, P., Pound, J. D., Tanaka, T., Walker, M. R., Artymiuk, P. J., Arata, Y., Burton, D. R., Jefferis, R., et al. (1991) · The Journal of Immunology · doi:10.4049/jimmunol.147.8.2657 · Cited by 212
Marketing approval of mogamulizumab
Beck, A., & Reichert, J. M. (2012) · mAbs · doi:10.4161/mabs.20996 · Cited by 211
Engineered Antibodies of IgG1/IgG3 Mixed Isotype with Enhanced Cytotoxic Activities
Natsume, A., In, M., Takamura, H., Nakagawa, T., Shimizu, Y., Kitajima, K., Wakitani, M., Ohta, S., Satoh, M., Shitara, K., et al. (2008) · Cancer Research · doi:10.1158/0008-5472.can-07-6297 · Cited by 194
Aglycosylation of human IgG1 and IgG3 monoclonal antibodies can eliminate recognition by human cells expressing FcγRI and/or FcγRII receptors
Walker, M. R., Lund, J., Thompson, K. M., & Jefferis, R. (1989) · Biochemical Journal · doi:10.1042/bj2590347 · Cited by 191
Delineation of the amino acid residues involved in transcytosis and catabolism of mouse IgG1
Medesan, C., Matesoi, D., Radu, C., Ghetie, V, & Ward, E. S. (1997) · The Journal of Immunology · doi:10.4049/jimmunol.158.5.2211 · Cited by 175
Inhibitory ITAMs as novel regulators of immunity
Blank, U., Launay, P., Benhamou, M., & Monteiro, R. C. (2009) · Immunological Reviews · doi:10.1111/j.1600-065x.2009.00832.x · Cited by 175
FACTORS CONTROLLING SERUM γ-GLOBULIN CONCENTRATION
Fahey, J. L., & ROBINSON, A. G. (1963) · The Journal of Experimental Medicine · doi:10.1084/jem.118.5.845 · Cited by 173
Structural Basis for FcγRIIa Recognition of Human IgG and Formation of Inflammatory Signaling Complexes
Ramsland, P. A., Farrugia, W., Bradford, T. M., Sardjono, C. T., Esparon, S. E., Trist, H. M., Powell, M. S., Tan, P. S., Cendron, A. C., Wines, B. D., et al. (2011) · The Journal of Immunology · doi:10.4049/jimmunol.1101467 · Cited by 168
The Immunologic Functions of the Neonatal Fc Receptor for IgG
Räth, T., Kuo, T. T., Baker, K., Qiao, S., Kobayashi, K., Yoshida, M., Roopenian, D. C., Fiebiger, E., Lencer, W. I., & Blumberg, R. S. (2012) · Journal of Clinical Immunology · doi:10.1007/s10875-012-9768-y · Cited by 162
An engineered Fc variant of an IgG eliminates all immune effector functions via structural perturbations
Vafa, O., Gilliland, G. L., Brezski, R. J., Strake, B., Wilkinson, T., Lacy, E. R., Scallon, B. J., Teplyakov, A., Malia, T., & Strohl, W. R. (2013) · Methods · doi:10.1016/j.ymeth.2013.06.035 · Cited by 158
Self-citation
Structural basis for binding of human IgG1 to its high-affinity human receptor FcγRI
Kiyoshi, M., Caaveiro, J. M. M., Kawai, T., Tashiro, S., Ide, T., Asaoka, Y., Hatayama, K., & Tsumoto, K. (2015) · Nature Communications · doi:10.1038/ncomms7866 · Cited by 155
Structure of FcγRI in complex with Fc reveals the importance of glycan recognition for high-affinity IgG binding
Lu, J., Chu, J., Zou, Z., Hamacher, N. B., Rixon, M. W., & Sun, P. D. (2015) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1418812112 · Cited by 153
Inhibition of B cell receptor-mediated activation of primary human B cells by coengagement of CD19 and FcγRIIb with Fc-engineered antibodies
Chu, S. Y., Voštiar, I., Karki, S., Moore, G. L., Lazar, G. A., Pong, E., Joyce, P. F., Szymkowski, D. E., & Desjarlais, J. R. (2008) · Molecular Immunology · doi:10.1016/j.molimm.2008.06.027 · Cited by 153
The IgG Fc Contains Distinct Fc Receptor (FcR) Binding Sites: The Leukocyte Receptors FcγRI and FcγRIIa Bind to a Region in the Fc Distinct from That Recognized by Neonatal FcR and Protein A
Wines, B. D., Powell, M. S., Parren, P. W. H. I., Barnes, N. C., & Hogarth, P. M. (2000) · The Journal of Immunology · doi:10.4049/jimmunol.164.10.5313 · Cited by 152
Identification of the Fc gamma receptor class I binding site in human IgG through the use of recombinant IgG1/IgG2 hybrid and point-mutated antibodies.
Chappel, M. S., Isenman, D. E., Everett, M., Xu, Y. Y., Dorrington, K. J., & Klein, M. (1991) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.88.20.9036 · Cited by 131
Engineered antibody Fc variant with selectively enhanced FcγRIIb binding over both FcγRIIaR131 and FcγRIIaH131
Mimoto, F., Katada, H., Kadono, S., Igawa, T., Kuramochi, T., Muraoka, M., Wada, Y., Haraya, K., Miyazaki, T., & Hattori, K. (2013) · Protein Engineering Design and Selection · doi:10.1093/protein/gzt022 · Cited by 127
Localisation of the monocyte-binding region on human immunoglobulin G
Woof, J. M., Partridge, L. J., Jefferis, R., & Burton, D. R. (1986) · Molecular Immunology · doi:10.1016/0161-5890(86)90059-3 · Cited by 120
Effect of a single amino acid mutation on the activating and immunosuppressive properties of a "humanized" OKT3 monoclonal antibody
Alegre, M. L. S., Collins, A., Pulito, V. L., Brosius, R., Olson, W. C., Zivin, R. A., Knowles, R. W., Thistlethwaite, J. R., Jolliffe, L. K., & Bluestone, J. A. (1992) · The Journal of Immunology · doi:10.4049/jimmunol.148.11.3461 · Cited by 116
Association of Polymorphisms in FCGR2A and FCGR3A With Degree of Trastuzumab Benefit in the Adjuvant Treatment of ERBB2/HER2–Positive Breast Cancer
Gavin, P. G., Song, N., Kim, S. R., Lipchik, C., Johnson, N. L., Bandos, H., Finnigan, M., Rastogi, P., Fehrenbacher, L., Mamounas, E. P., et al. (2016) · JAMA Oncology · doi:10.1001/jamaoncol.2016.4884 · Cited by 115
Effects of altered FcγR binding on antibody pharmacokinetics in cynomolgus monkeys
Leabman, M. K., Meng, Y. G., Kelley, R. F., DeForge, L. E., Cowan, K. J., & Iyer, S. (2013) · mAbs · doi:10.4161/mabs.26436 · Cited by 110
Regulation of complement and modulation of its activity in monoclonal antibody therapy of cancer
Meyer, S., Leusen, J. H. W., & Boross, P. (2014) · mAbs · doi:10.4161/mabs.29670 · Cited by 110
IgG2m4, an engineered antibody isotype with reduced Fc function
An, Z., Forrest, G., Moore, R., Cukan, M. C., Haytko, P., Huang, L., Vitelli, S., Zhao, J. Z., Lü, P., Hua, J., et al. (2009) · mAbs · doi:10.4161/mabs.1.6.10185 · Cited by 104
Structural characterization of a mutated, ADCC-enhanced human Fc fragment
Oganesyan, V., Damschroder, M. M., Leach, W., Wu, H., & Dall’Acqua, W. F. (2008) · Molecular Immunology · doi:10.1016/j.molimm.2007.10.042 · Cited by 89
Immunoglobulin isotype knowledge and application to Fc engineering
Brezski, R. J., & Georgiou, G. (2016) · Current Opinion in Immunology · doi:10.1016/j.coi.2016.03.002 · Cited by 86
Self-citation
Evidence of NI‐0101 pharmacological activity, an anti‐TLR4 antibody, in a randomized phase I dose escalation study in healthy volunteers receiving LPS
Monnet, E., Lapeyre, G., van Poelgeest, E. P., Jacqmin, P., de Graaf, K., Reijers, J. A. A., Moerland, M., Burggraaf, J., & de Min, C. (2016) · Clinical Pharmacology & Therapeutics · doi:10.1002/cpt.522 · Cited by 79
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Authors: Wang, X., Mathieu, M., & Brezski, R. J.
Affiliations: Genentech (US)
Corresponding author: Brezski, Randall J.
ORCID: Wang, Xinhua
Brezski, Randall J.
Venue: Protein & Cell
Publisher: Oxford University Press (OUP)
Published: 2017-10-06
Volume: 9
Issue: 1
Pages: 63-73
ISSN: 1674-800X (ISSN-L)
1674-8018
DOI: 10.1007/s13238-017-0473-8
PMC: PMC5777978
OpenAlex: W2763907629
Cited by: 356
References: 95
Citations by year: 2026: 28 · 2025: 41 · 2024: 57 · 2023: 35 · 2022: 50 · 2021: 44 · 2020: 44 · 2019: 43 · 2018: 13 · 2017: 1
FWCI: 4.22
Type: journal article
Language: en
Open access: gold
doi.org
Licence: cc-by
creativecommons.org/licenses/by/4.0 (unspecified)
Locations: Protein & Cell (publishedVersion, cc-by)
Europe PMC (PubMed Central) (publishedVersion, cc-by)
PubMed Central (publishedVersion, cc-by)
PubMed (publishedVersion)
DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
Topics: Life Sciences › Immunology and Microbiology › Immunology › Monoclonal and Polyclonal Antibodies Research
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein purification and stability
Life Sciences › Immunology and Microbiology › Immunology › Immune Cell Function and Interaction
Keywords: antibody effector functions, human IgG1, therapeutic monoclonal antibodies, antibody engineering, immune effector mechanisms, antibody safety, antibody efficacy
MeSH terms: Animals, Antibodies, Monoclonal, Antigens, Complement System Proteins, Humans, Immunoglobulin G, Receptors, Fc, Protein Engineering

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IgG Fc engineering to modulate antibody effector functions

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