IgG Fc domains that bind C1q but not effector Fcγ receptors delineate the importance of complement-mediated effector functions

Lee, Chang-Han; Romain, Gabrielle; Yan, Wupeng; Watanabe, Makiko; Charab, Wissam; Todorova, Biliana; Lee, Jiwon; Triplett, Kendra; Donkor, Moses; Lungu, Oana I.; Lux, Anja; Marshall, Nicholas; Lindorfer, Margaret A.; Goff, Odile Richard-Le; Balbino, Bianca; Kang, Tae Hyun; Tanno, Hidetaka; Delidakis, George; Alford, Corrine; Taylor, Ronald P.; Nimmerjahn, Falk; Varadarajan, Navin; Bruhns, Pierre; Zhang, Yan Jessie; Georgiou, George

doi:10.1038/ni.3770

IgG Fc domains that bind C1q but not effector Fcγ receptors delineate the importance of complement-mediated effector functions

Journal Article · Mon Jun 12 00:00:00 EDT 2017 · Nature Immunology

DOI:https://doi.org/10.1038/ni.3770· OSTI ID:1433698

^[1]; Romain, Gabrielle ^[2]; ^[1]; Watanabe, Makiko ^[1]; Charab, Wissam ^[1]; Todorova, Biliana ^[3]; Lee, Jiwon ^[1]; Triplett, Kendra ^[1]; Donkor, Moses ^[4]; Lungu, Oana I. ^[1]; Lux, Anja ^[5]; Marshall, Nicholas ^[6]; Lindorfer, Margaret A. ^[7]; Goff, Odile Richard-Le ^[3]; Balbino, Bianca ^[8]; Kang, Tae Hyun ^[1]; Tanno, Hidetaka ^[1]; Delidakis, George ^[1]; Alford, Corrine ^[1]; ^[9] more »

Univ. of Texas, Austin, TX (United States)
Univ. of Houston, TX (United States)
Inst. Pasteur, Paris (France)
MedImmune, Gaithersburg, MD (United States); Univ. of Texas, Austin, TX (United States)
Univ. of Erlangen-Nürnberg (Germany)
Dept. of Biochemical Engineering and Structure, Merck, NJ (United States); Univ. of Texas, Austin, TX (United States)
Univ. of Virginia of Medicine, Charlottesville, VA (United States)
Inst. Pasteur, Paris (France); INSERM, Paris (France); Univ. Pierre et Marie Curie, Paris (France)
Univ. of Virginia School of Medicine, Charlottesville, VA (United States)

Engineered crystallizable fragment (Fc) regions of antibody domains, which assume a unique and unprecedented asymmetric structure within the homodimeric Fc polypeptide, enable completely selective binding to the complement component C1q and activation of complement via the classical pathway without any concomitant engagement of the Fcγ receptor (FcγR). We used the engineered Fc domains to demonstrate in vitro and in mouse models that for therapeutic antibodies, complement-dependent cell-mediated cytotoxicity (CDCC) and complement-dependent cell-mediated phagocytosis (CDCP) by immunological effector molecules mediated the clearance of target cells with kinetics and efficacy comparable to those of the FcγR-dependent effector functions that are much better studied, while they circumvented certain adverse reactions associated with FcγR engagement. Here, collectively, our data highlight the importance of CDCC and CDCP in monoclonal-antibody function and provide an experimental approach for delineating the effect of complement-dependent effector-cell engagement in various therapeutic settings.

View Accepted Manuscript (DOE)

Research Organization:: Argonne National Laboratory (ANL), Argonne, IL (United States)

Sponsoring Organization:: USDOE Office of Science (SC), Basic Energy Sciences (BES) (SC-22); National Inst. of Health

Grant/Contract Number:: AC02-05CH11231

OSTI ID:: 1433698

Journal Information:: Nature Immunology, Journal Name: Nature Immunology Journal Issue: 8 Vol. 18; ISSN 1529-2908

Publisher:: Nature Research, Springer NatureCopyright Statement

Country of Publication:: United States

Language:: ENGLISH

References (57)

Activation of mouse complement by monoclonal mouse antibodies Neuberger, Michael S.; Rajewsky, Klaus European Journal of Immunology, Vol. 11, Issue 12 https://doi.org/10.1002/eji.1830111212	journal	January 1981
Structural Analysis of Human IgG-Fc Glycoforms Reveals a Correlation Between Glycosylation and Structural Integrity Krapp, S.; Mimura, Y.; Jefferis, R. Journal of Molecular Biology, Vol. 325, Issue 5 https://doi.org/10.1016/S0022-2836(02)01250-0	journal	January 2003
[20] Processing of X-ray diffraction data collected in oscillation mode Otwinowski, Zbyszek; Minor, Wladek Macromolecular Crystallography Part A, 307-326 https://doi.org/10.1016/S0076-6879(97)76066-X	book	January 1997
Immune evasion of tumor cells using membrane-bound complement regulatory proteins Gorter, Arko; Meri, Seppo Immunology Today, Vol. 20, Issue 12 https://doi.org/10.1016/S0167-5699(99)01537-6	journal	December 1999
Mechanism of action of therapeutic monoclonal antibodies: Promises and pitfalls of in vitro and in vivo assays Golay, Josée; Introna, Martino Archives of Biochemistry and Biophysics, Vol. 526, Issue 2 https://doi.org/10.1016/j.abb.2012.02.011	journal	October 2012
Differential Fc-Receptor Engagement Drives an Anti-tumor Vaccinal Effect DiLillo, David J.; Ravetch, Jeffrey V. Cell, Vol. 161, Issue 5 https://doi.org/10.1016/j.cell.2015.04.016	journal	May 2015
IgGA: A “Cross-Isotype” Engineered Human Fc Antibody Domain that Displays Both IgG-like and IgA-like Effector Functions Kelton, William; Mehta, Nishant; Charab, Wissam Chemistry & Biology, Vol. 21, Issue 12 https://doi.org/10.1016/j.chembiol.2014.10.017	journal	December 2014
Harnessing Fc receptor biology in the design of therapeutic antibodies Sondermann, Peter; Szymkowski, David E. Current Opinion in Immunology, Vol. 40 https://doi.org/10.1016/j.coi.2016.03.005	journal	June 2016
Expression and regulation of complement receptors by human natural killer cells Min, Xiaoyun; Liu, Chengfei; Wei, Yang Immunobiology, Vol. 219, Issue 9 https://doi.org/10.1016/j.imbio.2014.03.018	journal	September 2014
Complement-Mediated Regulation of Metabolism and Basic Cellular Processes Hess, Christoph; Kemper, Claudia Immunity, Vol. 45, Issue 2 https://doi.org/10.1016/j.immuni.2016.08.003	journal	August 2016
Inference of Macromolecular Assemblies from Crystalline State Krissinel, Evgeny; Henrick, Kim Journal of Molecular Biology, Vol. 372, Issue 3 https://doi.org/10.1016/j.jmb.2007.05.022	journal	September 2007
Immunoglobulin G1 Fc Domain Motions: Implications for Fc Engineering Frank, Martin; Walker, Ross C.; Lanzilotta, William N. Journal of Molecular Biology, Vol. 426, Issue 8 https://doi.org/10.1016/j.jmb.2014.01.011	journal	April 2014
Atomic resolution model of the antibody Fc interaction with the complement C1q component Schneider, Sebastian; Zacharias, Martin Molecular Immunology, Vol. 51, Issue 1 https://doi.org/10.1016/j.molimm.2012.02.111	journal	May 2012
Highly reduced binding to high and low affinity mouse Fc gamma receptors by L234A/L235A and N297A Fc mutations engineered into mouse IgG2a Arduin, E.; Arora, S.; Bamert, P. R. Molecular Immunology, Vol. 63, Issue 2 https://doi.org/10.1016/j.molimm.2014.09.017	journal	February 2015
An engineered Fc variant of an IgG eliminates all immune effector functions via structural perturbations Vafa, Omid; Gilliland, Gary L.; Brezski, Randall J. Methods, Vol. 65, Issue 1 https://doi.org/10.1016/j.ymeth.2013.06.035	journal	January 2014
The role of complement in mAb-based therapies of cancer Taylor, Ronald P.; Lindorfer, Margaret A. Methods, Vol. 65, Issue 1 https://doi.org/10.1016/j.ymeth.2013.07.027	journal	January 2014
Revisiting the Role of Glycosylation in the Structure of Human IgG Fc Borrok, M. Jack; Jung, Sang Taek; Kang, Tae Hyun ACS Chemical Biology, Vol. 7, Issue 9 https://doi.org/10.1021/cb300130k	journal	June 2012
Effective Phagocytosis of Low Her2 Tumor Cell Lines with Engineered, Aglycosylated IgG Displaying High FcγRIIa Affinity and Selectivity Jung, Sang Taek; Kelton, William; Kang, Tae Hyun ACS Chemical Biology, Vol. 8, Issue 2 https://doi.org/10.1021/cb300455f	journal	October 2012
Proteome-wide Detection and Quantitative Analysis of Irreversible Cysteine Oxidation Using Long Column UPLC-pSRM Lee, Chia-Fang; Paull, Tanya T.; Person, Maria D. Journal of Proteome Research, Vol. 12, Issue 10 https://doi.org/10.1021/pr400201d	journal	September 2013
The binding site for C1q on IgG Duncan, Alexander R.; Winter, Greg Nature, Vol. 332, Issue 6166 https://doi.org/10.1038/332738a0	journal	April 1988
Free R value: a novel statistical quantity for assessing the accuracy of crystal structures Brünger, Axel T. Nature, Vol. 355, Issue 6359 https://doi.org/10.1038/355472a0	journal	January 1992
Complement and its role in innate and adaptive immune responses Dunkelberger, Jason R.; Song, Wen-Chao Cell Research, Vol. 20, Issue 1 https://doi.org/10.1038/cr.2009.139	journal	December 2009
Complement: a key system for immune surveillance and homeostasis Ricklin, Daniel; Hajishengallis, George; Yang, Kun Nature Immunology, Vol. 11, Issue 9 https://doi.org/10.1038/ni.1923	journal	August 2010
Type I and type II Fc receptors regulate innate and adaptive immunity Pincetic, Andrew; Bournazos, Stylianos; DiLillo, David J. Nature Immunology, Vol. 15, Issue 8 https://doi.org/10.1038/ni.2939	journal	July 2014
Building better monoclonal antibody-based therapeutics Weiner, George J. Nature Reviews Cancer, Vol. 15, Issue 6 https://doi.org/10.1038/nrc3930	journal	May 2015
Anchored periplasmic expression, a versatile technology for the isolation of high-affinity antibodies from Escherichia coli-expressed libraries Harvey, B. R.; Georgiou, G.; Hayhurst, A. Proceedings of the National Academy of Sciences, Vol. 101, Issue 25 https://doi.org/10.1073/pnas.0400187101	journal	June 2004
Structure of FcγRI in complex with Fc reveals the importance of glycan recognition for high-affinity IgG binding Lu, Jinghua; Chu, Jonathan; Zou, Zhongcheng Proceedings of the National Academy of Sciences, Vol. 112, Issue 3 https://doi.org/10.1073/pnas.1418812112	journal	January 2015
Complement-dependent cellular cytotoxicity: lymphoblastoid lines that activate complement component 3 (C3) and express C3 receptors have increased sensitivity to lymphocyte-mediated lysis in the presence of fresh human serum. Ramos, O. F.; Sarmay, G.; Klein, E. Proceedings of the National Academy of Sciences, Vol. 82, Issue 16 https://doi.org/10.1073/pnas.82.16.5470	journal	August 1985
Activatory and Inhibitory Fcγ Receptors Augment Rituximab-mediated Internalization of CD20 Independent of Signaling via the Cytoplasmic Domain Vaughan, Andrew T.; Chan, Claude H. T.; Klein, Christian Journal of Biological Chemistry, Vol. 290, Issue 9 https://doi.org/10.1074/jbc.M114.593806	journal	January 2015
The Crystal Structure of the Globular Head of Complement Protein C1q Provides a Basis for Its Versatile Recognition Properties Gaboriaud, Christine; Juanhuix, Jordi; Gruez, Arnaud Journal of Biological Chemistry, Vol. 278, Issue 47 https://doi.org/10.1074/jbc.M307764200	journal	September 2003
Automated profiling of individual cell–cell interactions from high-throughput time-lapse imaging microscopy in nanowell grids (TIMING) Merouane, Amine; Rey-Villamizar, Nicolas; Lu, Yanbin Bioinformatics, Vol. 31, Issue 19 https://doi.org/10.1093/bioinformatics/btv355	journal	June 2015
Phaser crystallographic software McCoy, Airlie J.; Grosse-Kunstleve, Ralf W.; Adams, Paul D. Journal of Applied Crystallography, Vol. 40, Issue 4 https://doi.org/10.1107/S0021889807021206	journal	July 2007
Maximum-likelihood density modification Terwilliger, Thomas C. Acta Crystallographica Section D Biological Crystallography, Vol. 56, Issue 8 https://doi.org/10.1107/S0907444900005072	journal	August 2000
MolProbity : all-atom structure validation for macromolecular crystallography Chen, Vincent B.; Arendall, W. Bryan; Headd, Jeffrey J. Acta Crystallographica Section D Biological Crystallography, Vol. 66, Issue 1 https://doi.org/10.1107/S0907444909042073	journal	December 2009
PHENIX: a comprehensive Python-based system for macromolecular structure solution Adams, Paul D.; Afonine, Pavel V.; Bunkóczi, Gábor Acta Crystallographica Section D Biological Crystallography, Vol. 66, Issue 2, p. 213-221 https://doi.org/10.1107/S0907444909052925	journal	January 2010
Features and development of Coot Emsley, P.; Lohkamp, B.; Scott, W. G. Acta Crystallographica Section D Biological Crystallography, Vol. 66, Issue 4 https://doi.org/10.1107/S0907444910007493	journal	March 2010
Overview of the CCP 4 suite and current developments Winn, Martyn D.; Ballard, Charles C.; Cowtan, Kevin D. Acta Crystallographica Section D Biological Crystallography, Vol. 67, Issue 4 https://doi.org/10.1107/S0907444910045749	journal	March 2011
Mouse and human FcR effector functions Bruhns, Pierre; Jönsson, Friederike Immunological Reviews, Vol. 268, Issue 1 https://doi.org/10.1111/imr.12350	journal	October 2015
Monoclonal antibodies targeting CD38 in hematological malignancies and beyond van de Donk, Niels W. C. J.; Janmaat, Maarten L.; Mutis, Tuna Immunological Reviews, Vol. 270, Issue 1 https://doi.org/10.1111/imr.12389	journal	February 2016
Complement Is Activated by IgG Hexamers Assembled at the Cell Surface Diebolder, C. A.; Beurskens, F. J.; de Jong, R. N. Science, Vol. 343, Issue 6176 https://doi.org/10.1126/science.1248943	journal	March 2014
Role of Antibody and Complement in the Immune Clearance and Destruction of Erythrocytes II. MOLECULAR NATURE OF IgG AND IgM COMPLEMENT-FIXING SITES AND EFFECTS OF THEIR INTERACTION WITH SERUM Schreiber, Alan D.; Frank, Michael M. Journal of Clinical Investigation, Vol. 51, Issue 3 https://doi.org/10.1172/JCI106847	journal	March 1972
FcγRIV is a mouse IgE receptor that resembles macrophage FcεRI in humans and promotes IgE-induced lung inflammation Mancardi, David A.; Iannascoli, Bruno; Hoos, Sylviane Journal of Clinical Investigation, Vol. 118, Issue 11 https://doi.org/10.1172/JCI36452	journal	November 2008
Characterization of new human CD20 monoclonal antibodies with potent cytolytic activity against non-Hodgkin lymphomas Teeling, J. L. Blood, Vol. 104, Issue 6 https://doi.org/10.1182/blood-2004-01-0039	journal	September 2004
NK-cell activation and antibody-dependent cellular cytotoxicity induced by rituximab-coated target cells is inhibited by the C3b component of complement Wang, Siao-Yi; Racila, Emilian; Taylor, Ronald P. Blood, Vol. 111, Issue 3 https://doi.org/10.1182/blood-2007-02-074716	journal	February 2008
Specificity and affinity of human Fcγ receptors and their polymorphic variants for human IgG subclasses Bruhns, Pierre; Iannascoli, Bruno; England, Patrick Blood, Vol. 113, Issue 16 https://doi.org/10.1182/blood-2008-09-179754	journal	April 2009
Fc gamma receptor IIb on target B cells promotes rituximab internalization and reduces clinical efficacy Lim, Sean H.; Vaughan, Andrew T.; Ashton-Key, Margaret Blood, Vol. 118, Issue 9 https://doi.org/10.1182/blood-2011-01-330357	journal	September 2011
Properties of mouse and human IgG receptors and their contribution to disease models Bruhns, Pierre Blood, Vol. 119, Issue 24 https://doi.org/10.1182/blood-2012-01-380121	journal	June 2012
Antibody Fc engineering improves frequency and promotes kinetic boosting of serial killing mediated by NK cells Romain, Gabrielle; Senyukov, Vladimir; Rey-Villamizar, Nicolas Blood, Vol. 124, Issue 22 https://doi.org/10.1182/blood-2014-04-569061	journal	November 2014
Therapeutic activity of humanized anti-CD20 monoclonal antibody and polymorphism in IgG Fc receptor FcγRIIIa gene Cartron, Guillaume; Dacheux, Laurent; Salles, Gilles Blood, Vol. 99, Issue 3 https://doi.org/10.1182/blood.V99.3.754	journal	February 2002
Binding of Submaximal C1q Promotes Complement-Dependent Cytotoxicity (CDC) of B Cells Opsonized with Anti-CD20 mAbs Ofatumumab (OFA) or Rituximab (RTX): Considerably Higher Levels of CDC Are Induced by OFA than by RTX Pawluczkowycz, Andrew W.; Beurskens, Frank J.; Beum, Paul V. The Journal of Immunology, Vol. 183, Issue 1 https://doi.org/10.4049/jimmunol.0900632	journal	June 2009
Impact of Immune Complex Size and Glycosylation on IgG Binding to Human FcγRs Lux, Anja; Yu, Xiaojie; Scanlan, Chris N. The Journal of Immunology, Vol. 190, Issue 8 https://doi.org/10.4049/jimmunol.1200501	journal	March 2013
Ofatumumab Is More Efficient than Rituximab in Lysing B Chronic Lymphocytic Leukemia Cells in Whole Blood and in Combination with Chemotherapy Bologna, Luca; Gotti, Elisa; Da Roit, Fabio The Journal of Immunology, Vol. 190, Issue 1 https://doi.org/10.4049/jimmunol.1202645	journal	December 2012
Mapping of the C1q Binding Site on Rituxan, a Chimeric Antibody with a Human IgG1 Fc Idusogie, Esohe E.; Presta, Leonard G.; Gazzano-Santoro, Helene The Journal of Immunology, Vol. 164, Issue 8 https://doi.org/10.4049/jimmunol.164.8.4178	journal	April 2000
Complement Activation Determines the Therapeutic Activity of Rituximab In Vivo Di Gaetano, Nicola; Cittera, Elena; Nota, Rachele The Journal of Immunology, Vol. 171, Issue 3 https://doi.org/10.4049/jimmunol.171.3.1581	journal	July 2003
Rituximab Infusion Promotes Rapid Complement Depletion and Acute CD20 Loss in Chronic Lymphocytic Leukemia Kennedy, Adam D.; Beum, Paul V.; Solga, Michael D. The Journal of Immunology, Vol. 172, Issue 5 https://doi.org/10.4049/jimmunol.172.5.3280	journal	February 2004
The Biological Activity of Human CD20 Monoclonal Antibodies Is Linked to Unique Epitopes on CD20 Teeling, Jessica L.; Mackus, Wendy J. M.; Wiegman, Luus J. J. M. The Journal of Immunology, Vol. 177, Issue 1 https://doi.org/10.4049/jimmunol.177.1.362	journal	June 2006
Complement Activation on B Lymphocytes Opsonized with Rituximab or Ofatumumab Produces Substantial Changes in Membrane Structure Preceding Cell Lysis Beum, Paul V.; Lindorfer, Margaret A.; Beurskens, Frank The Journal of Immunology, Vol. 181, Issue 1 https://doi.org/10.4049/jimmunol.181.1.822	journal	June 2008

Cited By (25)

FHR4‐based immunoconjugates direct complement‐dependent cytotoxicity and phagocytosis towards HER2‐positive cancer cells Seguin‐Devaux, Carole; Plesseria, Jean‐Marc; Verschueren, Charlène Molecular Oncology, Vol. 13, Issue 12 https://doi.org/10.1002/1878-0261.12554	journal	September 2019
An engineered human Fc domain that behaves like a pH-toggle switch for ultra-long circulation persistence Lee, Chang-Han; Kang, Tae Hyun; Godon, Ophélie Nature Communications, Vol. 10, Issue 1 https://doi.org/10.1038/s41467-019-13108-2	journal	November 2019
Progress and Challenges in the Design and Clinical Development of Antibodies for Cancer Therapy Almagro, Juan C.; Daniels-Wells, Tracy R.; Perez-Tapia, Sonia Mayra Frontiers in Immunology, Vol. 8 https://doi.org/10.3389/fimmu.2017.01751	journal	January 2018
Potential of Murine IgG1 and Human IgG4 to Inhibit the Classical Complement and Fcγ Receptor Activation Pathways Lilienthal, Gina-Maria; Rahmöller, Johann; Petry, Janina Frontiers in Immunology, Vol. 9 https://doi.org/10.3389/fimmu.2018.00958	journal	May 2018
Structural Immunology of Complement Receptors 3 and 4 Vorup-Jensen, Thomas; Jensen, Rasmus Kjeldsen Frontiers in Immunology, Vol. 9 https://doi.org/10.3389/fimmu.2018.02716	journal	November 2018
The Emerging Role of Complement Proteins as a Target for Therapy of IgA Nephropathy Rizk, Dana V.; Maillard, Nicolas; Julian, Bruce A. Frontiers in Immunology, Vol. 10 https://doi.org/10.3389/fimmu.2019.00504	journal	March 2019
An Engineered Human Fc variant With Exquisite Selectivity for FcγRIIIaV158 Reveals That Ligation of FcγRIIIa Mediates Potent Antibody Dependent Cellular Phagocytosis With GM-CSF-Differentiated Macrophages Kang, Tae Hyun; Lee, Chang-Han; Delidakis, George Frontiers in Immunology, Vol. 10 https://doi.org/10.3389/fimmu.2019.00562	journal	March 2019
Deciphering Fc-mediated Antiviral Antibody Functions in Animal Models Schmaljohn, Alan L.; Orlandi, Chiara; Lewis, George K. Frontiers in Immunology, Vol. 10 https://doi.org/10.3389/fimmu.2019.01602	journal	July 2019
Infusion Reactions Associated with the Medical Application of Monoclonal Antibodies: The Role of Complement Activation and Possibility of Inhibition by Factor H Fülöp, Tamás; Mészáros, Tamás; Kozma, Gergely Antibodies, Vol. 7, Issue 1 https://doi.org/10.3390/antib7010014	journal	March 2018
Targeting IgG in Arthritis: Disease Pathways and Therapeutic Avenues Nandakumar, Kutty International Journal of Molecular Sciences, Vol. 19, Issue 3 https://doi.org/10.3390/ijms19030677	journal	February 2018
Understudied Factors Influencing Fc-Mediated Immune Responses against Viral Infections Anand, Sai Priya; Finzi, Andrés Vaccines, Vol. 7, Issue 3 https://doi.org/10.3390/vaccines7030103	journal	August 2019
Additional file 1 of An engineered Fc fusion protein that targets antigen-specific T cells and autoantibodies mitigates autoimmune disease Janakiraman, Mathangi; Leliavski, Alexei; Varadarajulu, Jeeva figshare https://doi.org/10.6084/m9.figshare.24761307.v1	image	January 2023
Efficient Innate Immune Killing of Cancer Cells Triggered by Cell‐Surface Anchoring of Multivalent Antibody‐Recruiting Polymers Uvyn, Annemiek; De Coen, Ruben; Gruijs, Mandy Angewandte Chemie, Vol. 131, Issue 37 https://doi.org/10.1002/ange.201905093	journal	July 2019
Efficient Innate Immune Killing of Cancer Cells Triggered by Cell‐Surface Anchoring of Multivalent Antibody‐Recruiting Polymers Uvyn, Annemiek; De Coen, Ruben; Gruijs, Mandy Angewandte Chemie International Edition, Vol. 58, Issue 37 https://doi.org/10.1002/anie.201905093	journal	July 2019
Identification of tumor-reactive B cells and systemic IgG in breast cancer based on clonal frequency in the sentinel lymph node McDaniel, Jonathan R.; Pero, Stephanie C.; Voss, William N. Cancer Immunology, Immunotherapy, Vol. 67, Issue 5 https://doi.org/10.1007/s00262-018-2123-2	journal	February 2018
Context-dependent roles of complement in cancer Roumenina, Lubka T.; Daugan, Marie V.; Petitprez, Florent Nature Reviews Cancer, Vol. 19, Issue 12 https://doi.org/10.1038/s41568-019-0210-0	journal	October 2019
Through the barricades: overcoming the barriers to effective antibody-based cancer therapeutics Dalziel, Martin; Beers, Stephen A.; Cragg, Mark S. Glycobiology, Vol. 28, Issue 9 https://doi.org/10.1093/glycob/cwy043	journal	June 2018
Identification of Tumor-Reactive B Cells and Systemic IgG in Breast Cancer Based on Clonal Frequency in the Sentinel Lymph Node McDaniel, Jonathan R.; Pero, Stephanie C.; Voss, William N. https://doi.org/10.1101/212308	posted_content	November 2017
Structural analysis of glycoproteins: building N-linked glycans with Coot Emsley, Paul; Crispin, Max Acta Crystallographica Section D Structural Biology, Vol. 74, Issue 4 https://doi.org/10.1107/s2059798318005119	journal	April 2018
The protective potential of Fc‐mediated antibody functions against influenza virus and other viral pathogens Vanderven, Hillary A.; Kent, Stephen J. Immunology & Cell Biology, Vol. 98, Issue 4 https://doi.org/10.1111/imcb.12312	journal	February 2020
A Restricted Role for FcγR in the Regulation of Adaptive Immunity. Fransen, Marieke F.; Benonisson, Hreinn; Van Maren, Wendy W. Apollo - University of Cambridge Repository https://doi.org/10.17863/cam.30215	text	January 2018
Therapeutic Antibodies: What Have We Learnt from Targeting CD20 and Where Are We Going? Marshall, Michael J. E.; Stopforth, Richard J.; Cragg, Mark S. Frontiers in Immunology, Vol. 8 https://doi.org/10.3389/fimmu.2017.01245	journal	October 2017
Antibody Structure and Function: The Basis for Engineering Therapeutics Chiu, Mark L.; Goulet, Dennis R.; Teplyakov, Alexey Antibodies, Vol. 8, Issue 4 https://doi.org/10.3390/antib8040055	journal	December 2019
A Restricted Role for FcγR in the Regulation of Adaptive Immunity Fransen, Marieke F.; Benonisson, Hreinn; van Maren, Wendy W. The Journal of Immunology, Vol. 200, Issue 8 https://doi.org/10.4049/jimmunol.1700429	journal	March 2018
High FcγR Expression on Intratumoral Macrophages Enhances Tumor-Targeting Antibody Therapy Benonisson, Hreinn; Sow, Heng Sheng; Breukel, Cor The Journal of Immunology, Vol. 201, Issue 12 https://doi.org/10.4049/jimmunol.1800700	journal	November 2018

Similar Records

Glycosylation-dependent opsonophagocytic activity of staphylococcal protein A antibodies

Journal Article · Thu Aug 27 00:00:00 EDT 2020 · Proceedings of the National Academy of Sciences of the United States of America · OSTI ID:1815835

Therapeutic efficacy of a potent anti-Venezuelan equine encephalitis virus antibody is contingent on Fc effector function

Journal Article · Tue Jan 02 23:00:00 EST 2024 · MAbs · OSTI ID:2469756

Related Subjects

59 BASIC BIOLOGICAL SCIENCES
Cancer therapy
Cellular immunity
Complement cascade
X-ray crystallography

IgG Fc domains that bind C1q but not effector Fcγ receptors delineate the importance of complement-mediated effector functions

Citation Formats

References (57)

Cited By (25)

Similar Records

Related Subjects