Developing the IVIG biomimetic, Hexa-Fc, for drug and vaccine applications
Open accessAbstract
The remarkable clinical success of Fc-fusion proteins has driven intense investigation for even more potent replacements. Using quality-by-design (QbD) approaches, we generated hexameric-Fc (hexa-Fc), a ~20 nm oligomeric Fc-based scaffold that we here show binds low-affinity inhibitory receptors (FcRL5, FcγRIIb and DC-SIGN) with high avidity and specificity, whilst eliminating significant clinical limitations of monomeric Fc-fusions for vaccine and/or cancer therapies, in particular their poor ability to activate complement. Mass spectroscopy of hexa-Fc reveals high-mannose, low-sialic acid content, suggesting that interactions with these receptors are influenced by the mannose-containing Fc. Molecular dynamics (MD) simulations provides insight into the mechanisms of hexa-Fc interaction with these receptors and reveals an unexpected orientation of high-mannose glycans on the human Fc that provides greater accessibility to potential binding partners. Finally, we show that this biosynthetic nanoparticle can be engineered to enhance interactions with the human neonatal Fc receptor (FcRn) without loss of the oligomeric structure, a crucial modification for these molecules in therapy and/or vaccine strategies where a long plasma half-life is critical.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
The hexameric IgG-Fc fusion protein-scaffold binds low-affinity receptors FcRL5, FcγRIIb, and DC-SIGN with high specificity and avidity.
“This protein-scaffold was later shown to also bind low-affinity receptors (FcRL5, FcγRIIb, and DC-SIGN) with high specificity and avidity [119].”
From Glycoengineering Chinese hamster ovary cells: a short history (2021) · cites this paper as [119]
The Results sections on FcRL5/FcγRIIb and DC-SIGN report binding of hexa-Fc to all three receptors. Control-receptor tests and valence-dependent binding support selectivity and an avidity effect, but the DC-SIGN Results describe its binding affinity as moderate (KD 1.26 μM), not uniformly high; the claim overstates the strength of binding across the three receptors. (LLM, conf=0.85)
Experimental — accuracy not yet measured
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
Comparison of simple potential functions for simulating liquid water
Jorgensen, W. L., Chandrasekhar, J., Madura, J., Impey, R., & Klein, M. (1983) · The Journal of Chemical Physics · doi:10.1063/1.445869 · Cited by 38,335 · see citing works
Scalable molecular dynamics with NAMD
Phillips, J. C., Braun, R., Wang, W., Gumbart, J., Tajkhorshid, E., Villa, E., Chipot, C., Skeel, R. D., Kalé, L., & Schulten, K. (2005) · Journal of Computational Chemistry · doi:10.1002/jcc.20289 · Cited by 16,914 · see citing works
SWISS‐MODEL and the Swiss‐Pdb Viewer: An environment for comparative protein modeling
Guex, N., & Peitsch, M. (1997) · Electrophoresis · doi:10.1002/elps.1150181505 · Cited by 11,589 · see citing works
Best, R. B., Zhu, X., Shim, J., Lopes, P. E. M., Mittal, J., Feig, M., & MacKerell, A. D. (2012) · Journal of Chemical Theory and Computation · doi:10.1021/ct300400x · Cited by 4,472 · see citing works
DC-SIGN, a dendritic cell-specific HIV-1-binding protein that enhances trans-infection of T cells
Geijtenbeek, T. B. H., Kwon, D. S., Torensma, R., van Vliet, S. J., van Duijnhoven, G. C. F., Middel, J., Cornelissen, I. L. M. H. A., Nottet, H. S. L. M., KewalRamani, V. N., Littman, D. R., et al. (2000) · Cell · doi:10.1016/s0092-8674(00)80694-7 · Cited by 2,447 · see citing works
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 · see citing works
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 1,164 · see citing works
GlycoWorkbench: A Tool for the Computer-Assisted Annotation of Mass Spectra of Glycans
Ceroni, A., Maaß, K., Geyer, H., Geyer, R., Dell, A., & Haslam, S. M. (2008) · Journal of Proteome Research · doi:10.1021/pr7008252 · Cited by 1,059 · see citing works
Self-citationAnti-inflammatory Activity of IVIG Mediated Through the Inhibitory Fc Receptor
Samuelsson, A., Towers, T. L., & Ravetch, J. V. (2001) · Science · doi:10.1126/science.291.5503.484 · Cited by 1,051 · see citing works
Intravenous immunoglobulin therapy: how does IgG modulate the immune system?
Schwab, I., & Nimmerjahn, F. (2013) · Nature reviews. Immunology · doi:10.1038/nri3401 · Cited by 818 · see citing works
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 · see citing works
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 719 · see citing works
Structural Basis for Selective Recognition of Oligosaccharides by DC-SIGN and DC-SIGNR
Feinberg, H., Mitchell, D. A., Drickamer, K., & Weis, W. I. (2001) · Science · doi:10.1126/science.1066371 · Cited by 678 · see citing works
Self-citationEnhanced 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 657 · see citing works
Intravenous gammaglobulin suppresses inflammation through a novel TH2 pathway
Anthony, R. M., Kobayashi, T., Wermeling, F., & Ravetch, J. (2011) · Nature · doi:10.1038/nature10134 · Cited by 625 · see citing works
Designing CD4 immunoadhesins for AIDS therapy
Capon, D. J., Chamow, S. M., Mordenti, J. J., Marsters, S. A., Gregory, T. J., Mitsuya, H., Byrn, R. A., Lucas, C., Wurm, F. M., Groopman, J. E., et al. (1989) · Nature · doi:10.1038/337525a0 · Cited by 616 · see citing works
Gringhuis, S. I., den Dunnen, J., Litjens, M., Hof, B. V. H., van Kooyk, Y., & Geijtenbeek, T. B. H. (2007) · Immunity · doi:10.1016/j.immuni.2007.03.012 · Cited by 588 · see citing works
Regulation of B Lymphocyte Responses to Foreign and Self-Antigens by the CD19/CD21 Complex
Fearon, D. T., Carroll, M. C., & Carroll, M. C. (2000) · Annual Review of Immunology · doi:10.1146/annurev.immunol.18.1.393 · Cited by 529 · see citing works
Type I and type II Fc receptors regulate innate and adaptive immunity
Pincetic, A., Bournazos, S., DiLillo, D. J., Maamary, J., Wang, T. T., Dahan, R., Fiebiger, B. M., & Ravetch, J. V. (2014) · Nature Immunology · doi:10.1038/ni.2939 · Cited by 504 · see citing works
A Novel Mechanism of Carbohydrate Recognition by the C-type Lectins DC-SIGN and DC-SIGNR
Mitchell, D. A., Fadden, A. J., & Drickamer, K. (2001) · Journal of Biological Chemistry · doi:10.1074/jbc.m104565200 · Cited by 502 · see citing works
Self-citationFc‐fusion proteins: new developments and future perspectives
Czajkowsky, D. M., Hu, J., Shao, Z., & Pleass, R. J. (2012) · EMBO Molecular Medicine · doi:10.1002/emmm.201201379 · Cited by 477 · see citing works
Self-citationRefined Structure of an Intact IgG2a Monoclonal Antibody ,
Harris, L. J., Larson, S. B., Hasel, K. W., & McPherson, A. (1997) · Biochemistry · doi:10.1021/bi962514+ · Cited by 451 · see citing works
Gringhuis, S. I., den Dunnen, J., Litjens, M., van der Vlist, M., & Geijtenbeek, T. B. H. (2009) · Nature Immunology · doi:10.1038/ni.1778 · Cited by 444 · see citing works
Human antibody–Fc receptor interactions illuminated by crystal structures
Woof, J. M., & Burton, D. R. (2004) · Nature reviews. Immunology · doi:10.1038/nri1266 · Cited by 388 · see citing works
Regulation of Humoral Immunity by Complement
Carroll, M. C., & Isenman, D. E. (2012) · Immunity · doi:10.1016/j.immuni.2012.08.002 · Cited by 386 · see citing works
Daëron, M., Malbec, O., Latour, S., Arock, M., & Fridman, W. H. (1995) · Journal of Clinical Investigation · doi:10.1172/jci117701 · Cited by 360 · see citing works
Raghavan, M., Bonagura, V. R., Morrison, S. L., & Bjorkman, P. J. (1995) · Biochemistry · doi:10.1021/bi00045a005 · Cited by 317 · see citing works
Hezareh, M., Hessell, A. J., Jensen, R. C., van de Winkel, J. G. J., & Parren, P. W. H. I. (2001) · Journal of Virology · doi:10.1128/jvi.75.24.12161-12168.2001 · Cited by 294 · see citing works
Specificity of DC‐SIGN for mannose‐ and fucose‐containing glycans
van Liempt, E., Bank, C. M. C., Mehta, P., García-Vallejo, J. J., Kawar, Z. S., Geyer, R., Alvarez, R., Cummings, R. D., van Kooyk, Y., & van Die, I. (2006) · FEBS Letters · doi:10.1016/j.febslet.2006.10.009 · Cited by 286 · see citing works
Fc-fusion proteins and FcRn: structural insights for longer-lasting and more effective therapeutics
Räth, T., Baker, K., Dumont, J. A., Peters, R., Jiang, H., Qiao, S., Lencer, W. I., Pierce, G. F., & Blumberg, R. S. (2013) · Critical Reviews in Biotechnology · doi:10.3109/07388551.2013.834293 · Cited by 282 · see citing works
An Engineered Human IgG1 Antibody with Longer Serum Half-Life
Hinton, P. R., Xiong, J. M., Johlfs, M. G., Tang, M. T., Keller, S., & Tsurushita, N. (2006) · The Journal of Immunology · doi:10.4049/jimmunol.176.1.346 · Cited by 282 · see citing works
Structural Comparison of Fucosylated and Nonfucosylated Fc Fragments of Human Immunoglobulin G1
Matsumiya, S., Yamaguchi, Y., Saito, J., Nagano, M., Sasakawa, H., Otaki, S., Satoh, M., Shitara, K., & Kato, K. (2007) · Journal of Molecular Biology · doi:10.1016/j.jmb.2007.02.034 · Cited by 278 · see citing works
Impact of Immune Complex Size and Glycosylation on IgG Binding to Human FcγRs
Lux, A., Yu, X., Scanlan, C. N., & Nimmerjahn, F. (2013) · The Journal of Immunology · doi:10.4049/jimmunol.1200501 · Cited by 272 · see citing works
What's fueling the biotech engine—2012 to 2013
Aggarwal, S. (2014) · Nature Biotechnology · doi:10.1038/nbt.2794 · Cited by 254 · see citing works
Contrasting IgG structures reveal extreme asymmetry and flexibility.
Saphire, E., Stanfield, R., Maxcrispin, M., Parren, P., Rudd, P., Dwek, R., Burton, D., & Wilson, I. A. G. (2002) · Journal of Molecular Biology · doi:10.1016/s0022-2836(02)00244-9 · Cited by 249 · see citing works
Correlation between segmental flexibility and effector function of antibodies
Oi, V. T., Vuong, T. M., Hardy, R. R., Reidler, J. A., Dangl, J. L., Herzenberg, L. A., & Stryer, L. (1984) · Nature · doi:10.1038/307136a0 · Cited by 229 · see citing works
Jo, S., Song, K., Desaire, H., MacKerell, A. D., & Im, W. (2011) · Journal of Computational Chemistry · doi:10.1002/jcc.21886 · Cited by 226 · see citing works
Davis, R. S. (2007) · Annual Review of Immunology · doi:10.1146/annurev.immunol.25.022106.141541 · Cited by 225 · see citing works
General mechanism for modulating immunoglobulin effector function
Sondermann, P., Pincetic, A., Maamary, J., Lammens, K., & Ravetch, J. V. (2013) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1307864110 · Cited by 218 · see citing works
Becer, C. R., Gibson, M. I., Geng, J., Ilyas, R., Wallis, R., Mitchell, D. A., & Haddleton, D. M. (2010) · Journal of the American Chemical Society · doi:10.1021/ja1056714 · Cited by 195 · see citing works
Self-citationExpression Profile of FcγRIIb on Leukocytes and Its Dysregulation in Systemic Lupus Erythematosus
Su, K., Yang, H., Li, X., Li, X., Gibson, A., Cafardi, J. M., Zhou, T., Edberg, J. C., & Kimberly, R. P. (2007) · The Journal of Immunology · doi:10.4049/jimmunol.178.5.3272 · Cited by 179 · see citing works
Efficient mucosal vaccination mediated by the neonatal Fc receptor
Ye, L., Zeng, R., Bai, Y., Roopenian, D. C., & Zhu, X. (2011) · Nature Biotechnology · doi:10.1038/nbt.1742 · Cited by 157 · see citing works
Baker, K., Räth, T., Flak, M. B., Arthur, J. C., Chen, Z., Glickman, J. N., Zlobec, I., Karamitopoulou, E., Stachler, M. D., Odze, R. D., et al. (2013) · Immunity · doi:10.1016/j.immuni.2013.11.003 · Cited by 142 · see citing works
Kurosaki, T., Gander, I., & Ravetch, J. V. (1991) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.88.9.3837 · Cited by 136 · see citing works
Cutting Edge: Human FcRL4 and FcRL5 Are Receptors for IgA and IgG
Wilson, T. J., Fuchs, A. G., & Colonna, M. (2012) · The Journal of Immunology · doi:10.4049/jimmunol.1102651 · Cited by 134 · see citing works
Self-citationYu, X., Vasiljević, S., Mitchell, D. A., Crispin, M., & Scanlan, C. N. (2013) · Journal of Molecular Biology · doi:10.1016/j.jmb.2013.02.006 · Cited by 128 · see citing works
Self-citationThe inhibitory potential of Fc receptor homolog 4 on memory B cells
Ehrhardt, G. R. A., Davis, R. S., Hsu, J. T., Leu, C., Ehrhardt, A., & Cooper, M. D. (2003) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1935944100 · Cited by 127 · see citing works
Londrigan, S. L., Turville, S. G., Tate, M. D., Deng, Y., Brööks, A. G., & Reading, P. C. (2010) · Journal of Virology · doi:10.1128/jvi.01705-10 · Cited by 125 · see citing works
An endoglycosidase with alternative glycan specificity allows broadened glycoprotein remodelling.
Goodfellow, J., Baruah, K., Yamamoto, K., Bonomelli, C., Krishna, B., Harvey, D., Crispin, M., Scanlan, C. N., & Davis, B. (2012) · Journal of the American Chemical Society · doi:10.1021/ja301334b · Cited by 123 · see citing works
Leontyev, D., Katsman, Y., Ma, X., Miescher, S., Käsermann, F., & Branch, D. R. (2012) · Transfusion · doi:10.1111/j.1537-2995.2011.03517.x · Cited by 119 · see citing works
Ido, S., Kimiya, H., Kobayashi, K., Kominami, H., Matsushige, K., & Yamada, H. (2014) · Nature Materials · doi:10.1038/nmat3847 · Cited by 116 · see citing works
IVI g‐mediated amelioration of ITP in mice is dependent on sialic acid and SIGNR 1
Schwab, I., Biburger, M., Krönke, G., Schett, G. A., & Nimmerjahn, F. (2012) · European Journal of Immunology · doi:10.1002/eji.201142260 · Cited by 110 · see citing works
Fc receptor-like 5 inhibits B cell activation via SHP-1 tyrosine phosphatase recruitment
Haga, C. L., Ehrhardt, G. R. A., Boohaker, R. J., Davis, R. S., & Cooper, M. D. (2007) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0703354104 · Cited by 107 · see citing works
Crispin, M., Yu, X., & Bowden, T. A. (2013) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1310657110 · Cited by 89 · see citing works
Crystal Structure of Fcγ Receptor I and Its Implication in High Affinity γ-Immunoglobulin Binding
Lu, J., Ellsworth, J. L., Hamacher, N. B., Oak, A. S. W., & Sun, P. D. (2011) · Journal of Biological Chemistry · doi:10.1074/jbc.m111.257550 · Cited by 87 · see citing works
Human Fc Receptor–Like 5 Binds Intact IgG via Mechanisms Distinct from Those of Fc Receptors
Franco, A., Damdinsuren, B., Ise, T., Dement-Brown, J., Li, H., Nagata, S., & Tolnay, M. (2013) · The Journal of Immunology · doi:10.4049/jimmunol.1202860 · Cited by 85 · see citing works
Polymeric human Fc-fusion proteins with modified effector functions
Mekhaiel, D. N. A., Czajkowsky, D. M., Andersen, J. T., Shi, J., El-Faham, M., Doenhoff, M., McIntosh, R. S., Sandlie, I., He, J., Hu, J., et al. (2011) · Scientific Reports · doi:10.1038/srep00124 · Cited by 85 · see citing works
Self-citationSmith, R. I. F., Coloma, M. J., & Morrison, S. L. (1995) · The Journal of Immunology · doi:10.4049/jimmunol.154.5.2226 · Cited by 81 · see citing works
Targeting the Neonatal Fc Receptor for Antigen Delivery Using Engineered Fc Fragments
Mi, W., Wanjie, S., Lo, S., Gan, Z., Pickl-Herk, B., Ober, R. J., & Ward, E. S. (2008) · The Journal of Immunology · doi:10.4049/jimmunol.181.11.7550 · Cited by 71 · see citing works
Crispin, M., Bowden, T. A., Coles, C. H., Harlos, K., Aricescu, A. R., Harvey, D. J., Stuart, D. I., & Jones, E. Y. (2009) · Journal of Molecular Biology · doi:10.1016/j.jmb.2009.02.033 · Cited by 66 · see citing works
Mass Spectrometric Analysis of Mutant Mice
North, S. J., Jang‐Lee, J., Harrison, R., Canis, K., Ismail, M. N., Trollope, A., Antonopoulos, A., Pang, P., Grassi, P., Chalabi, S., et al. (2010) · Methods in enzymology on CD-ROM/Methods in enzymology · doi:10.1016/s0076-6879(10)78002-2 · Cited by 64 · see citing works
Self-citationJain, A. K., Olsen, H. S., Vyzasatya, R., Burch, E. E., Sakoda, Y., Mérigeon, E. Y., Cai, L., Lu, C., Tan, M. T., Tamada, K., et al. (2012) · Arthritis Research & Therapy · doi:10.1186/ar4024 · Cited by 59 · see citing works
Wilson, T. J., Gilfillan, S., & Colonna, M. (2010) · The Journal of Immunology · doi:10.4049/jimmunol.1001428 · Cited by 38 · see citing works
Self-citationEpstein-Barr virus nuclear antigen 2 induces FcRH5 expression through CBF1
Mohan, J., Dement-Brown, J., Maier, S., Ise, T., Kempkes, B., & Tolnay, M. (2006) · Blood · doi:10.1182/blood-2005-09-3815 · Cited by 31 · see citing works
Cutting Edge: FcR-Like 5 on Innate B Cells Is Targeted by a Poxvirus MHC Class I-Like Immunoevasin
Campbell, J. A., Davis, R. S., Lilly, L. M., Fremont, D. H., French, A. R., & Carayannopoulos, L. N. (2010) · The Journal of Immunology · doi:10.4049/jimmunol.1000240 · Cited by 30 · see citing works
The role of carbohydrate in the assembly and function of polymeric IgG
Coloma, M. J., Clift, A., Wims, L. A., & Morrison, S. L. (2000) · Molecular Immunology · doi:10.1016/s0161-5890(01)00024-4 · Cited by 22 · see citing works
Lu, J., Ellsworth, J. L., Hamacher, N. B., Oak, A. S. W., & Sun, P. D. (2011) · Journal of Biological Chemistry · doi:10.2210/pdb3rjd/pdb · Cited by 11 · see citing works
Flagged first, then by citations
1 of the 68 references couldn’t be matched to a known paper.
Cited by
Sorted by citations
Conceptual Approaches to Modulating Antibody Effector Functions and Circulation Half-Life
Saunders, K. O. (2019) · Frontiers in Immunology · doi:10.3389/fimmu.2019.01296 · Cited by 315 · see citing works
Next-generation Fc receptor–targeting biologics for autoimmune diseases
Zuercher, A. W., Spirig, R., Morelli, A. B., Rowe, T., & Käsermann, F. (2019) · Autoimmunity Reviews · doi:10.1016/j.autrev.2019.102366 · Cited by 156 · see citing works
Sonneveld, M. E., Natunen, S., Sainio, S., Koeleman, C. A. M., Holst, S., Dekkers, G., Koelewijn, J. M., Partanen, J., van der Schoot, C. E., Wuhrer, M., et al. (2016) · British Journal of Haematology · doi:10.1111/bjh.14053 · Cited by 102 · see citing works
Shock, A., Humphreys, D. P., & Nimmerjahn, F. (2020) · Journal of Allergy and Clinical Immunology · doi:10.1016/j.jaci.2020.06.036 · Cited by 73 · see citing works
Ortiz, D. F., Lansing, J. C., Rutitzky, L. I., Kurtagic, E., Prod’homme, T., Choudhury, A., Washburn, N., Bhatnagar, N., Beneduce, C., Holte, K., et al. (2016) · Science Translational Medicine · doi:10.1126/scitranslmed.aaf9418 · Cited by 71 · see citing works
Human DC-SIGN and CD23 do not interact with human IgG
Temming, A. R., Dekkers, G., van de Bovenkamp, F. S., Plomp, H. R., Bentlage, A. E. H., Szittner, Z., Derksen, N. I. L., Wuhrer, M., Rispens, T., & Vidarsson, G. (2019) · Scientific Reports · doi:10.1038/s41598-019-46484-2 · Cited by 55 · see citing works
Qureshi, O. S., Rowley, T. F., Junker, F., Peters, S. J., Crilly, S., Compson, J. E., Eddleston, A., Björkelund, H., Greenslade, K. J., Parkinson, M. D., et al. (2017) · Scientific Reports · doi:10.1038/s41598-017-17255-8 · Cited by 53 · see citing works
Site-SpecificN-Glycosylation of Recombinant Pentameric and Hexameric Human IgM
Moh, E. S. X., Lin, C.-H., Thaysen‐Andersen, M., & Packer, N. H. (2016) · Journal of the American Society for Mass Spectrometry · doi:10.1007/s13361-016-1378-0 · Cited by 51 · see citing works
rIgG1 Fc Hexamer Inhibits Antibody-Mediated Autoimmune Disease via Effects on Complement and FcγRs
Spirig, R., Campbell, I. K., Koernig, S., Chen, C., Lewis, B. J. B., Butcher, R. E., Muir, I. L., Taylor, S., Chia, J., Leong, D., et al. (2018) · The Journal of Immunology · doi:10.4049/jimmunol.1701171 · Cited by 48 · see citing works
Glycoengineering Chinese hamster ovary cells: a short history
Donini, R., Haslam, S. M., & Kontoravdi, C. (2021) · Biochemical Society Transactions · doi:10.1042/bst20200840 · Cited by 37 · see citing works
Self-citationPleass, R. J., Moore, S. C., Stevenson, L., & Hviid, L. (2015) · Trends in Parasitology · doi:10.1016/j.pt.2015.09.007 · Cited by 36 · see citing works
Self-citationEnhanced FcRn-dependent transepithelial delivery of IgG by Fc-engineering and polymerization
Foss, S., Grevys, A., Sand, K. M. K., Bern, M., Blundell, P. A., Michaelsen, T. E., Pleass, R. J., Sandlie, I., & Andersen, J. T. (2015) · Journal of Controlled Release · doi:10.1016/j.jconrel.2015.12.033 · Cited by 36 · see citing works
Self-citationHarvey, D. J. (2021) · Mass Spectrometry Reviews · doi:10.1002/mas.21651 · Cited by 33 · see citing works
Tradtrantip, L., Felix, C. M., Spirig, R., Morelli, A. B., & Verkman, A. S. (2018) · Neuropharmacology · doi:10.1016/j.neuropharm.2018.02.002 · Cited by 30 · see citing works
Immunomodulatory and anti‐inflammatory properties of immunoglobulin G antibodies
Hematianlarki, M., & Nimmerjahn, F. (2024) · Immunological Reviews · doi:10.1111/imr.13404 · Cited by 29 · see citing works
Rowley, T. F., Peters, S. J., Aylott, M. C., Griffin, R., Davies, N. L., Healy, L. J., Cutler, R. M., Eddleston, A., Pither, T. L., Sopp, J. M., et al. (2018) · Communications Biology · doi:10.1038/s42003-018-0149-9 · Cited by 29 · see citing works
Blundell, P. A., Lu, D., Dell, A., Haslam, S., & Pleass, R. J. (2020) · The Journal of Immunology · doi:10.4049/jimmunol.1901145 · Cited by 29 · see citing works
Self-citationBlundell, P. A., Le, N. P. L., Allen, J., Watanabe, Y., & Pleass, R. J. (2017) · Journal of Biological Chemistry · doi:10.1074/jbc.m117.795047 · Cited by 26 · see citing works
Self-citationBosques, C. J., & Manning, A. M. (2016) · Autoimmunity Reviews · doi:10.1016/j.autrev.2016.07.035 · Cited by 25 · see citing works
Glycan-independent binding and internalization of human IgM to FCMR, its cognate cellular receptor
Lloyd, K. A., Wang, J., Urban, B. C., Czajkowsky, D. M., & Pleass, R. J. (2017) · Scientific Reports · doi:10.1038/srep42989 · Cited by 22 · see citing works
Self-citationThe therapeutic potential of sialylated Fc domains of human IgG
Pleass, R. J. (2021) · mAbs · doi:10.1080/19420862.2021.1953220 · Cited by 21 · see citing works
Self-citationDifferences in Immunoglobulin G Glycosylation Between Influenza and COVID-19 Patients
Batinjan, M. K.-G., Pribić, T., Vučković, F., Hadžibegović, I., Radovani, B., Jurin, I., Đerek, L., Huljev, E., Markotić, A., Lukšić, I., et al. (2022) · Engineering · doi:10.1016/j.eng.2022.08.007 · Cited by 20 · see citing works
IgG opsonization of merozoites: multiple immune mechanisms for malaria vaccine development
Hill, D. L., Schofield, L., & Wilson, D. W. (2017) · International Journal for Parasitology · doi:10.1016/j.ijpara.2017.05.004 · Cited by 20 · see citing works
Ohyama, Y., Nakajima, K., Renfrow, M. B., Novák, J., & Takahashi, K. (2020) · Expert Review of Proteomics · doi:10.1080/14789450.2020.1769479 · Cited by 19 · see citing works
Blundell, P. A., Lu, D., Wilkinson, M., Dell, A., Haslam, S., & Pleass, R. J. (2019) · The Journal of Immunology · doi:10.4049/jimmunol.1801337 · Cited by 11 · see citing works
Self-citationMultimerized IgG1 Fc molecule as an anti-inflammatory agent
Victor, E. S., & Bayry, J. (2018) · Nature Reviews Rheumatology · doi:10.1038/s41584-018-0013-9 · Cited by 9 · see citing works
Lewis, B. J. B., & Branch, D. R. (2020) · Pharmacology · doi:10.1159/000508239 · Cited by 7 · see citing works
Mechanisms of Action and Immunomodulation by IVIg
Lazarus, A. H. (2018) · Springer eBooks · doi:10.1007/978-3-319-68038-5_6 · Cited by 6 · see citing works
Scherg, F., Haag, F., & Krieger, T. (2019) · BMJ Case Reports · doi:10.1136/bcr-2018-227917 · Cited by 6 · see citing works
Anti-inflammatory Activity of IgG-Fc
Beneduce, C., Kurtagic, E., & Bosques, C. J. (2019) · Current topics in microbiology and immunology · doi:10.1007/82_2019_148 · Cited by 5 · see citing works
Baksmeier, C., Blundell, P. A., Steckel, J., Schultz, V., Gu, Q., Filipe, A. D. S., Kohl, A., Linnington, C., Lu, D., Dell, A., et al. (2021) · Immunology · doi:10.1111/imm.13341 · Cited by 5 · see citing works
Self-citationGenetic Divergence and Antibody Expression Influence the N‐Glycomes of CHO‐K1 and CHO‐S Cells
Donini, R., Blundell, P. A., Pleass, R. J., Lu, D., Dell, A., Kontoravdi, C., & Haslam, S. M. (2025) · Biotechnology and Bioengineering · doi:10.1002/bit.70045 · Cited by 3 · see citing works
Self-citationPinto, A. J., Chouquet, A., Bally, I., Rossi, V., Thielens, N. M., Dumestre‐Pérard, C., Kunert, R., Gaboriaud, C., Ling, W. L., & Reiser, J. (2025) · FEBS Journal · doi:10.1111/febs.70309 · Cited by 2 · see citing works
Tong, M., Liu, P., Li, C., Zhang, Z., Sun, W. F., Dong, P., Fan, N., Wang, X., Liu, J., Lv, C., et al. (2024) · Journal of Chemical Information and Modeling · doi:10.1021/acs.jcim.3c01584 · Cited by 1 · see citing works
Immunomodulation of immunothrombocytopenia
Nimmerjahn, F. (2016) · Seminars in Hematology · doi:10.1053/j.seminhematol.2016.04.004
Progress in immune-modulating biomaterials for complement system regulation
Abudousu, A., Tang, Y., Xiang, L., Wang, Z., Li, Y., Zhao, D., Mutailifu, M., Jiang, Q., Liu, B., & Cui, W. (2026) · Progress in Materials Science · doi:10.1016/j.pmatsci.2026.101765
Engineered Trivalent Human IgG1-Fc Proteins for Potent Complement Inhibition
Campbell, I. K., Ortiz, D., Bosques, C. J., Hardy, M. P., Tester, A., Tomasetig, V., Couto, D., Gentinetta, T., Pestel, S., Ponnuswamy, P., et al. (2026) · Cells · doi:10.3390/cells15131156
Fc and tailpiece determinants of IgM tailpiece-mediated IgG hexamerisationPreprint
Peters, S. J., Sopp, J. M., Ede, J., Ahdash, Z., Hailu, H., Hold, A., Holmes, B., Cragg, M. S., & Humphreys, D. (2026) · Research Square · doi:10.21203/rs.3.rs-10432191/v1
- Authors
- Czajkowsky, D. M., Andersen, J. T., Fuchs, A., Wilson, T. J., Mekhaiel, D., Colonna, M., He, J., Shao, Z., Mitchell, D. A., Wu, G., Dell, A., Haslam, S., Lloyd, K. A., Moore, S. C., Sandlie, I., Blundell, P. A., & Pleass, R. J.
- Affiliations
- Shanghai Jiao Tong University (CN)
- Oslo University Hospital (NO)
- Washington University in St. Louis (US)
- Liverpool School of Tropical Medicine (GB)
- University of Warwick (GB)
- Imperial College London (GB)
- Corresponding author
- Pleass, Richard J.
- ORCID
- Venue
- Scientific Reports
- Published
- 2015-04-27
- Volume
- 5
- Issue
- 1
- Pages
- 9526-9526
- ISSN
- 2045-2322 (ISSN-L)
- PMC
- PMC5224519
- OpenAlex
- W2090214639
- Cited by
- 38
- References
- 68
- Citations by year
- 2026: 3 · 2025: 2 · 2024: 2 · 2022: 1 · 2021: 4 · 2020: 4 · 2019: 6 · 2018: 5 · 2017: 4 · 2016: 5 · 2015: 2
- FWCI
- 4.32
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- Scientific Reports (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- LSTM Online Archive (Liverpool School of Tropical Medicine) (acceptedVersion)
- Digital Commons@Becker (Washington University School of Medicine) (submittedVersion)
- NORA - Norwegian Open Research Archives (submittedVersion, cc-by)
- Funders
- Royal Society
- University of Oxford
- National Natural Science Foundation of China (11374207, 21303104, 31370750, 91129000)
- Norges Forskningsråd (179573/V40, 230526, 179573, 230526/F20)
- Directorate for Biological Sciences
- Medical Research Council (MC_PC_12017)
- Engineering and Physical Sciences Research Council (987447)
- Biotechnology and Biological Sciences Research Council (BB/K016164/1, BB/F008309/1)
- Helse Sør-Øst RHF (179573/V40, 39375, 230526)
- Topics
- Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Monoclonal and Polyclonal Antibodies Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein purification and stability
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Viral Infectious Diseases and Gene Expression in Insects
- Keywords
- Fc fusion protein, biomimetic scaffolds, quality by design, FCRL5, FcγRIIB, DC-SIGN, complement activation, high-mannose glycans, sialic acid, neonatal Fc receptor, plasma half-life, vaccine adjuvants, cancer immunotherapy, nanoparticle drug delivery
- MeSH terms
- Carrier Proteins, Cells, Cultured, Half-Life, Humans, Immunoglobulin G, Immunoglobulin Fc Fragments, Leukocytes, Mononuclear, Protein Binding, Receptors, Fc, Vaccines, Histocompatibility Antigens Class I, Immunoglobulins, Intravenous, Biomimetics
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
