Review
. 2019 Apr; 10:481.
doi: 10.3389/fimmu.2019.00481.

Targeting the Antibody Checkpoints to Enhance Cancer Immunotherapy-Focus on FcγRIIB

Ingrid Teige 1 Linda Mårtensson 1 Björn L Frendéus 1 
Affiliations
  • PMID: 30930905
  •     109 References
  •     14 citations

Abstract

Immunotherapy with therapeutic antibodies has increased survival for patients with hematologic and solid cancers. Still, a significant fraction of patients fails to respond to therapy or acquire resistance. Understanding and overcoming mechanisms of resistance to antibody drugs, and in particular those common to antibody drugs as a class, is therefore highly warranted and holds promise to improve response rates, duration of response and potentially overall survival. Activating and inhibitory Fc gamma receptors (FcγR) are known to coordinately regulate therapeutic activity of tumor direct-targeting antibodies. Similar, but also divergent, roles for FcγRs in controlling efficacy of immune modulatory antibodies e.g., checkpoint inhibitors have been indicated from mouse studies, and were recently implicated in contributing to efficacy in the human clinical setting. Here we discuss evidence and mechanisms by which Fc gamma receptors-the "antibody checkpoints"-regulate antibody-induced antitumor immunity. We further discuss how targeted blockade of the sole known inhibitory antibody checkpoint FcγRIIB may help overcome resistance and boost activity of clinically validated and emerging antibodies in cancer immunotherapy.

Keywords: antibody checkpoint; cancer immunotherapy; drug resistance; fc gamma receptor; therapeutic antibody; tumor microenvironment.

Engagement of the OX-40 receptor in vivo enhances antitumor immunity.
A D Weinberg, M M Rivera, +7 authors, J Shields.
J Immunol, 2000 Feb 05; 164(4). PMID: 10657670
Highly Cited.
Inhibitory Fc receptors modulate in vivo cytotoxicity against tumor targets.
R A Clynes, T L Towers, L G Presta, J V Ravetch.
Nat Med, 2000 Mar 31; 6(4). PMID: 10742152
Highly Cited.
Therapeutic efficacy of OX-40 receptor antibody depends on tumor immunogenicity and anatomic site of tumor growth.
J Kjaergaard, J Tanaka, +3 authors, S Shu.
Cancer Res, 2000 Oct 18; 60(19). PMID: 11034096
IgG2a-mediated enhancement of antibody responses is dependent on FcRgamma+ bone marrow-derived cells.
T Diaz de Ståhl, B Heyman.
Scand J Immunol, 2001 Nov 07; 54(5). PMID: 11696201
Therapeutic activity of humanized anti-CD20 monoclonal antibody and polymorphism in IgG Fc receptor FcgammaRIIIa gene.
Guillaume Cartron, Laurent Dacheux, +4 authors, Hervé Watier.
Blood, 2002 Jan 25; 99(3). PMID: 11806974
Highly Cited.
The B7 family of ligands and its receptors: new pathways for costimulation and inhibition of immune responses.
Beatriz M Carreno, Mary Collins.
Annu Rev Immunol, 2002 Feb 28; 20. PMID: 11861596
Highly Cited. Review.
Lack of fucose on human IgG1 N-linked oligosaccharide improves binding to human Fcgamma RIII and antibody-dependent cellular toxicity.
Robert L Shields, Jadine Lai, +5 authors, Leonard G Presta.
J Biol Chem, 2002 May 03; 277(30). PMID: 11986321
Highly Cited.
Inducing tumor immunity through the selective engagement of activating Fcgamma receptors on dendritic cells.
Alexis M Kalergis, Jeffrey V Ravetch.
J Exp Med, 2002 Jun 19; 195(12). PMID: 12070293    Free PMC article.
Highly Cited.
Fc gamma Rs modulate cytotoxicity of anti-Fas antibodies: implications for agonistic antibody-based therapeutics.
Yuanyuan Xu, Alexander J Szalai, +5 authors, Robert P Kimberly.
J Immunol, 2003 Jul 09; 171(2). PMID: 12847219
Two immunoglobulin G fragment C receptor polymorphisms independently predict response to rituximab in patients with follicular lymphoma.
Wen-Kai Weng, Ronald Levy.
J Clin Oncol, 2003 Sep 17; 21(21). PMID: 12975461
Highly Cited.
FcgammaRIIB is differentially expressed during B cell maturation and in B-cell lymphomas.
Sophie Camilleri-Broët, Lydie Cassard, +6 authors, Catherine Sautès-Fridman.
Br J Haematol, 2003 Dec 17; 124(1). PMID: 14675408
The innate mononuclear phagocyte network depletes B lymphocytes through Fc receptor-dependent mechanisms during anti-CD20 antibody immunotherapy.
Junji Uchida, Yasuhito Hamaguchi, +4 authors, Thomas F Tedder.
J Exp Med, 2004 Jun 24; 199(12). PMID: 15210744    Free PMC article.
Highly Cited.
Concomitant tumor immunity to a poorly immunogenic melanoma is prevented by regulatory T cells.
Mary Jo Turk, José A Guevara-Patiño, +3 authors, Alan N Houghton.
J Exp Med, 2004 Sep 24; 200(6). PMID: 15381730    Free PMC article.
Highly Cited.
Selective blockade of inhibitory Fcgamma receptor enables human dendritic cell maturation with IL-12p70 production and immunity to antibody-coated tumor cells.
Kavita M Dhodapkar, Jacob L Kaufman, +6 authors, Madhav V Dhodapkar.
Proc Natl Acad Sci U S A, 2005 Feb 11; 102(8). PMID: 15703291    Free PMC article.
FcgammaRIV: a novel FcR with distinct IgG subclass specificity.
Falk Nimmerjahn, Pierre Bruhns, Ken Horiuchi, Jeffrey V Ravetch.
Immunity, 2005 Jul 26; 23(1). PMID: 16039578
Highly Cited.
Divergent immunoglobulin g subclass activity through selective Fc receptor binding.
Falk Nimmerjahn, Jeffrey V Ravetch.
Science, 2005 Dec 03; 310(5753). PMID: 16322460
Highly Cited.
Fcgamma receptors: old friends and new family members.
Falk Nimmerjahn, Jeffrey V Ravetch.
Immunity, 2006 Jan 18; 24(1). PMID: 16413920
Highly Cited. Review.
Engineered antibody Fc variants with enhanced effector function.
Greg A Lazar, Wei Dang, +11 authors, Bassil I Dahiyat.
Proc Natl Acad Sci U S A, 2006 Mar 16; 103(11). PMID: 16537476    Free PMC article.
Highly Cited.
CD32B, the human inhibitory Fc-gamma receptor IIB, as a target for monoclonal antibody therapy of B-cell lymphoma.
Christopher T Rankin, Maria-Concetta Veri, +10 authors, Ezio Bonvini.
Blood, 2006 Jun 08; 108(7). PMID: 16757681
Monoclonal antibodies capable of discriminating the human inhibitory Fcgamma-receptor IIB (CD32B) from the activating Fcgamma-receptor IIA (CD32A): biochemical, biological and functional characterization.
Maria-Concetta Veri, Sergey Gorlatov, +6 authors, Scott Koenig.
Immunology, 2007 Mar 28; 121(3). PMID: 17386079    Free PMC article.
Fc gamma receptor IIB on dendritic cells enforces peripheral tolerance by inhibiting effector T cell responses.
Dharmesh D Desai, Stephanie O Harbers, +5 authors, Raphael Clynes.
J Immunol, 2007 May 04; 178(10). PMID: 17475849
FCGR2A and FCGR3A polymorphisms associated with clinical outcome of epidermal growth factor receptor expressing metastatic colorectal cancer patients treated with single-agent cetuximab.
Wu Zhang, Michael Gordon, +10 authors, Heinz-Josef Lenz.
J Clin Oncol, 2007 Aug 21; 25(24). PMID: 17704420
Highly Cited.
Cetuximab for the treatment of colorectal cancer.
Derek J Jonker, Chris J O'Callaghan, +12 authors, Malcolm J Moore.
N Engl J Med, 2007 Nov 16; 357(20). PMID: 18003960
Highly Cited.
Immunoglobulin G fragment C receptor polymorphisms and clinical efficacy of trastuzumab-based therapy in patients with HER-2/neu-positive metastatic breast cancer.
Antonino Musolino, Nadia Naldi, +9 authors, Andrea Ardizzoni.
J Clin Oncol, 2008 Mar 19; 26(11). PMID: 18347005
Highly Cited.
OX40 triggering blocks suppression by regulatory T cells and facilitates tumor rejection.
Silvia Piconese, Barbara Valzasina, Mario P Colombo.
J Exp Med, 2008 Mar 26; 205(4). PMID: 18362171    Free PMC article.
Highly Cited.
OX40 agonist therapy enhances CD8 infiltration and decreases immune suppression in the tumor.
Michael J Gough, Carl E Ruby, +3 authors, Andrew D Weinberg.
Cancer Res, 2008 Jul 03; 68(13). PMID: 18593921
Monoclonal antibody therapy for B-cell non-Hodgkin's lymphoma.
Bruce D Cheson, John P Leonard.
N Engl J Med, 2008 Aug 09; 359(6). PMID: 18687642
Highly Cited. Review.
Optimization of antibody binding to FcgammaRIIa enhances macrophage phagocytosis of tumor cells.
John O Richards, Sher Karki, +3 authors, John R Desjarlais.
Mol Cancer Ther, 2008 Aug 30; 7(8). PMID: 18723496
Identification of a high affinity FcgammaRIIA-binding peptide that distinguishes FcgammaRIIA from FcgammaRIIB and exploits FcgammaRIIA-mediated phagocytosis and degradation.
Gøril Berntzen, Jan Terje Andersen, +6 authors, Inger Sandlie.
J Biol Chem, 2008 Oct 30; 284(2). PMID: 18957413
Specificity and affinity of human Fcgamma receptors and their polymorphic variants for human IgG subclasses.
Pierre Bruhns, Bruno Iannascoli, +4 authors, Marc Daëron.
Blood, 2008 Nov 20; 113(16). PMID: 19018092
Highly Cited.
Copy number variation at the FCGR locus includes FCGR3A, FCGR2C and FCGR3B but not FCGR2A and FCGR2B.
Willemijn B Breunis, Edwin van Mirre, +7 authors, Taco W Kuijpers.
Hum Mutat, 2009 Mar 25; 30(5). PMID: 19309690
Blockade of CTLA-4 on both effector and regulatory T cell compartments contributes to the antitumor activity of anti-CTLA-4 antibodies.
Karl S Peggs, Sergio A Quezada, +2 authors, James P Allison.
J Exp Med, 2009 Jul 08; 206(8). PMID: 19581407    Free PMC article.
Highly Cited.
Functional and clinical consequences of Fc receptor polymorphic and copy number variants.
S Bournazos, J M Woof, S P Hart, I Dransfield.
Clin Exp Immunol, 2009 Jul 17; 157(2). PMID: 19604264    Free PMC article.
Review.
Depletion of the C3 component of complement enhances the ability of rituximab-coated target cells to activate human NK cells and improves the efficacy of monoclonal antibody therapy in an in vivo model.
Siao-Yi Wang, Suresh Veeramani, +5 authors, George J Weiner.
Blood, 2009 Oct 07; 114(26). PMID: 19805620    Free PMC article.
Antigenic modulation limits the efficacy of anti-CD20 antibodies: implications for antibody selection.
Stephen A Beers, Ruth R French, +13 authors, Mark S Cragg.
Blood, 2010 Mar 13; 115(25). PMID: 20223920
Highly Cited.
Therapeutic control of B cell activation via recruitment of Fcgamma receptor IIb (CD32B) inhibitory function with a novel bispecific antibody scaffold.
Maria-Concetta Veri, Stephen Burke, +14 authors, Ezio Bonvini.
Arthritis Rheum, 2010 May 28; 62(7). PMID: 20506263
Improved survival with ipilimumab in patients with metastatic melanoma.
F Stephen Hodi, Steven J O'Day, +26 authors, Walter J Urba.
N Engl J Med, 2010 Jun 08; 363(8). PMID: 20525992    Free PMC article.
Highly Cited.
The therapeutic effect of anti-HER2/neu antibody depends on both innate and adaptive immunity.
SaeGwang Park, Zhujun Jiang, +11 authors, Yang-Xin Fu.
Cancer Cell, 2010 Aug 17; 18(2). PMID: 20708157    Free PMC article.
Highly Cited.
An Fcγ receptor-dependent mechanism drives antibody-mediated target-receptor signaling in cancer cells.
Nicholas S Wilson, Becky Yang, +17 authors, Avi Ashkenazi.
Cancer Cell, 2011 Jan 22; 19(1). PMID: 21251615
Highly Cited.
The glycosyl phosphatidylinositol-linked Fc gamma RIIIPMN mediates transmembrane signaling events distinct from Fc gamma RII.
R P Kimberly, J W Ahlstrom, M E Click, J C Edberg.
J Exp Med, 1990 Apr 01; 171(4). PMID: 2139101    Free PMC article.
CD40 agonists alter tumor stroma and show efficacy against pancreatic carcinoma in mice and humans.
Gregory L Beatty, Elena G Chiorean, +10 authors, Robert H Vonderheide.
Science, 2011 Mar 26; 331(6024). PMID: 21436454    Free PMC article.
Highly Cited.
Ipilimumab plus dacarbazine for previously untreated metastatic melanoma.
Caroline Robert, Luc Thomas, +21 authors, Jedd D Wolchok.
N Engl J Med, 2011 Jun 07; 364(26). PMID: 21639810
Highly Cited.
Interaction with FcγRIIB is critical for the agonistic activity of anti-CD40 monoclonal antibody.
Ann L White, H T Claude Chan, +10 authors, Martin J Glennie.
J Immunol, 2011 Jul 12; 187(4). PMID: 21742972
Fc gamma receptor IIb on target B cells promotes rituximab internalization and reduces clinical efficacy.
Sean H Lim, Andrew T Vaughan, +13 authors, Martin J Glennie.
Blood, 2011 Jul 20; 118(9). PMID: 21768293
Inhibitory Fcγ receptor engagement drives adjuvant and anti-tumor activities of agonistic CD40 antibodies.
Fubin Li, Jeffrey V Ravetch.
Science, 2011 Aug 20; 333(6045). PMID: 21852502    Free PMC article.
Highly Cited.
HER2 therapy--an abundance of riches.
William J Gradishar.
N Engl J Med, 2011 Dec 14; 366(2). PMID: 22149874
Pertuzumab plus trastuzumab plus docetaxel for metastatic breast cancer.
José Baselga, Javier Cortés, +12 authors, CLEOPATRA Study Group.
N Engl J Med, 2011 Dec 14; 366(2). PMID: 22149875    Free PMC article.
Highly Cited.
Monocyte subsets responsible for immunoglobulin G-dependent effector functions in vivo.
Markus Biburger, Susanne Aschermann, +6 authors, Falk Nimmerjahn.
Immunity, 2011 Dec 16; 35(6). PMID: 22169040
Phenotypic variation in IgG receptors by nonclassical FCGR2C alleles.
Joris van der Heijden, Willemijn B Breunis, +3 authors, Taco W Kuijpers.
J Immunol, 2011 Dec 27; 188(3). PMID: 22198951
The blockade of immune checkpoints in cancer immunotherapy.
Drew M Pardoll.
Nat Rev Cancer, 2012 Mar 23; 12(4). PMID: 22437870    Free PMC article.
Highly Cited. Review.
Mouse model recapitulating human Fcγ receptor structural and functional diversity.
Patrick Smith, David J DiLillo, +2 authors, Jeffrey V Ravetch.
Proc Natl Acad Sci U S A, 2012 Apr 05; 109(16). PMID: 22474370    Free PMC article.
Highly Cited.
Anti-CD20 antibody therapy for B-cell lymphomas.
David G Maloney.
N Engl J Med, 2012 May 25; 366(21). PMID: 22621628
Highly Cited. Review.
Fcγ receptor IIb strongly regulates Fcγ receptor-facilitated T cell activation by dendritic cells.
Nadine van Montfoort, Peter A C 't Hoen, +5 authors, J Sjef Verbeek.
J Immunol, 2012 Jun 01; 189(1). PMID: 22649202
Safety, activity, and immune correlates of anti-PD-1 antibody in cancer.
Suzanne L Topalian, F Stephen Hodi, +27 authors, Mario Sznol.
N Engl J Med, 2012 Jun 05; 366(26). PMID: 22658127    Free PMC article.
Highly Cited.
Safety and activity of anti-PD-L1 antibody in patients with advanced cancer.
Julie R Brahmer, Scott S Tykodi, +23 authors, Jon M Wigginton.
N Engl J Med, 2012 Jun 05; 366(26). PMID: 22658128    Free PMC article.
Highly Cited.
Apoptotic and antitumor activity of death receptor antibodies require inhibitory Fcγ receptor engagement.
Fubin Li, Jeffrey V Ravetch.
Proc Natl Acad Sci U S A, 2012 Jun 23; 109(27). PMID: 22723355    Free PMC article.
FcγRIIb on liver sinusoidal endothelium clears small immune complexes.
Latha P Ganesan, Jonghan Kim, +5 authors, Clark L Anderson.
J Immunol, 2012 Oct 12; 189(10). PMID: 23053513    Free PMC article.
A critical review of the role of Fc gamma receptor polymorphisms in the response to monoclonal antibodies in cancer.
James D Mellor, Michael P Brown, +2 authors, Alexander Dobrovic.
J Hematol Oncol, 2013 Jan 05; 6. PMID: 23286345    Free PMC article.
Highly Cited. Review.
The high-affinity human IgG receptor FcγRI (CD64) promotes IgG-mediated inflammation, anaphylaxis, and antitumor immunotherapy.
David A Mancardi, Marcello Albanesi, +6 authors, Pierre Bruhns.
Blood, 2013 Jan 08; 121(9). PMID: 23293080
Depleting tumor-specific Tregs at a single site eradicates disseminated tumors.
Aurélien Marabelle, Holbrook Kohrt, +13 authors, Ronald Levy.
J Clin Invest, 2013 Jun 04; 123(6). PMID: 23728179    Free PMC article.
Highly Cited.
Oncology meets immunology: the cancer-immunity cycle.
Daniel S Chen, Ira Mellman.
Immunity, 2013 Jul 31; 39(1). PMID: 23890059
Highly Cited. Review.
Fc-dependent depletion of tumor-infiltrating regulatory T cells co-defines the efficacy of anti-CTLA-4 therapy against melanoma.
Tyler R Simpson, Fubin Li, +11 authors, Sergio A Quezada.
J Exp Med, 2013 Jul 31; 210(9). PMID: 23897981    Free PMC article.
Highly Cited.
Activating Fc γ receptors contribute to the antitumor activities of immunoregulatory receptor-targeting antibodies.
Yannick Bulliard, Rose Jolicoeur, +6 authors, Jennifer L Brogdon.
J Exp Med, 2013 Jul 31; 210(9). PMID: 23897982    Free PMC article.
Highly Cited.
Signatures of mutational processes in human cancer.
Ludmil B Alexandrov, Serena Nik-Zainal, +72 authors, Michael R Stratton.
Nature, 2013 Aug 16; 500(7463). PMID: 23945592    Free PMC article.
Highly Cited.
Glycoengineered CD20 antibody obinutuzumab activates neutrophils and mediates phagocytosis through CD16B more efficiently than rituximab.
Josée Golay, Fabio Da Roit, +5 authors, Martino Introna.
Blood, 2013 Oct 10; 122(20). PMID: 24106207
Highly Cited.
The mechanism of anti-CD20-mediated B cell depletion revealed by intravital imaging.
Fabricio Montalvao, Zacarias Garcia, +4 authors, Philippe Bousso.
J Clin Invest, 2013 Nov 02; 123(12). PMID: 24177426    Free PMC article.
Inhibitory FcγRIIb (CD32b) becomes activated by therapeutic mAb in both cis and trans and drives internalization according to antibody specificity.
Andrew T Vaughan, Chisako Iriyama, +8 authors, Mark S Cragg.
Blood, 2013 Nov 15; 123(5). PMID: 24227819
Obinutuzumab plus chlorambucil in patients with CLL and coexisting conditions.
Valentin Goede, Kirsten Fischer, +20 authors, Michael Hallek.
N Engl J Med, 2014 Jan 10; 370(12). PMID: 24401022
Highly Cited.
The function of Fcγ receptors in dendritic cells and macrophages.
Martin Guilliams, Pierre Bruhns, +2 authors, Bart N Lambrecht.
Nat Rev Immunol, 2014 Jan 22; 14(2). PMID: 24445665
Highly Cited. Review.
PI3Kδ inhibition by idelalisib in patients with relapsed indolent lymphoma.
Ajay K Gopal, Brad S Kahl, +19 authors, Gilles A Salles.
N Engl J Med, 2014 Jan 24; 370(11). PMID: 24450858    Free PMC article.
Highly Cited.
Sensitizing protective tumor microenvironments to antibody-mediated therapy.
Christian P Pallasch, Ilya Leskov, +15 authors, Michael T Hemann.
Cell, 2014 Feb 04; 156(3). PMID: 24485462    Free PMC article.
PD-1 blockade and OX40 triggering synergistically protects against tumor growth in a murine model of ovarian cancer.
Zhiqiang Guo, Xin Wang, +3 authors, Shulan Zhang.
PLoS One, 2014 Mar 04; 9(2). PMID: 24586709    Free PMC article.
Highly Cited.
OX40 engagement depletes intratumoral Tregs via activating FcγRs, leading to antitumor efficacy.
Yannick Bulliard, Rose Jolicoeur, +3 authors, Jennifer L Brogdon.
Immunol Cell Biol, 2014 Apr 16; 92(6). PMID: 24732076
Highly Cited.
Anti-CTLA-4 antibodies of IgG2a isotype enhance antitumor activity through reduction of intratumoral regulatory T cells.
Mark J Selby, John J Engelhardt, +4 authors, Alan J Korman.
Cancer Immunol Res, 2014 Apr 30; 1(1). PMID: 24777248
Highly Cited.
Contribution of Human FcγRs to Disease with Evidence from Human Polymorphisms and Transgenic Animal Studies.
Caitlin Gillis, Aurélie Gouel-Chéron, Friederike Jönsson, Pierre Bruhns.
Front Immunol, 2014 Jun 10; 5. PMID: 24910634    Free PMC article.
Review.
Anti-programmed-death-receptor-1 treatment with pembrolizumab in ipilimumab-refractory advanced melanoma: a randomised dose-comparison cohort of a phase 1 trial.
Caroline Robert, Antoni Ribas, +22 authors, Adil Daud.
Lancet, 2014 Jul 19; 384(9948). PMID: 25034862
Highly Cited.
Type I and type II Fc receptors regulate innate and adaptive immunity.
Andrew Pincetic, Stylianos Bournazos, +5 authors, Jeffrey V Ravetch.
Nat Immunol, 2014 Jul 22; 15(8). PMID: 25045879    Free PMC article.
Highly Cited. Review.
Expression of the inhibitory Fc gamma receptor IIB (FCGR2B, CD32B) on follicular lymphoma cells lowers the response rate to rituximab monotherapy (SAKK 35/98).
Chern Siang Lee, Margaret Ashton-Key, +5 authors, Peter Johnson.
Br J Haematol, 2014 Aug 22; 168(1). PMID: 25142001
How immunoglobulin G antibodies kill target cells: revisiting an old paradigm.
Markus Biburger, Anja Lux, Falk Nimmerjahn.
Adv Immunol, 2014 Sep 02; 124. PMID: 25175773
Review.
The programmed death-1 immune-suppressive pathway: barrier to antitumor immunity.
Suzanne Ostrand-Rosenberg, Lucas A Horn, Samuel T Haile.
J Immunol, 2014 Oct 05; 193(8). PMID: 25281753    Free PMC article.
Highly Cited. Review.
Nivolumab in previously untreated melanoma without BRAF mutation.
Caroline Robert, Georgina V Long, +25 authors, Paolo A Ascierto.
N Engl J Med, 2014 Nov 18; 372(4). PMID: 25399552
Highly Cited.
Dissecting the tumor myeloid compartment reveals rare activating antigen-presenting cells critical for T cell immunity.
Miranda L Broz, Mikhail Binnewies, +12 authors, Matthew F Krummel.
Cancer Cell, 2014 Dec 03; 26(5). PMID: 25446897    Free PMC article.
Highly Cited.
B7H1/CD80 interaction augments PD-1-dependent T cell apoptosis and ameliorates graft-versus-host disease.
Ruishu Deng, Kaniel Cassady, +6 authors, Defu Zeng.
J Immunol, 2014 Dec 10; 194(2). PMID: 25488990    Free PMC article.
Nivolumab versus chemotherapy in patients with advanced melanoma who progressed after anti-CTLA-4 treatment (CheckMate 037): a randomised, controlled, open-label, phase 3 trial.
Jeffrey S Weber, Sandra P D'Angelo, +25 authors, James Larkin.
Lancet Oncol, 2015 Mar 22; 16(4). PMID: 25795410
Highly Cited.
Immune checkpoint blockade: a common denominator approach to cancer therapy.
Suzanne L Topalian, Charles G Drake, Drew M Pardoll.
Cancer Cell, 2015 Apr 11; 27(4). PMID: 25858804    Free PMC article.
Highly Cited. Review.
Antagonistic human FcγRIIB (CD32B) antibodies have anti-tumor activity and overcome resistance to antibody therapy in vivo.
Ali Roghanian, Ingrid Teige, +29 authors, Mark S Cragg.
Cancer Cell, 2015 Apr 16; 27(4). PMID: 25873171
Nivolumab and ipilimumab versus ipilimumab in untreated melanoma.
Michael A Postow, Jason Chesney, +18 authors, F Stephen Hodi.
N Engl J Med, 2015 Apr 22; 372(21). PMID: 25891304    Free PMC article.
Highly Cited.
Melanoma-intrinsic β-catenin signalling prevents anti-tumour immunity.
Stefani Spranger, Riyue Bao, Thomas F Gajewski.
Nature, 2015 May 15; 523(7559). PMID: 25970248
Highly Cited.
Differential Fc-Receptor Engagement Drives an Anti-tumor Vaccinal Effect.
David J DiLillo, Jeffrey V Ravetch.
Cell, 2015 May 16; 161(5). PMID: 25976835    Free PMC article.
Highly Cited.
Combined Nivolumab and Ipilimumab or Monotherapy in Untreated Melanoma.
James Larkin, Vanna Chiarion-Sileni, +28 authors, Jedd D Wolchok.
N Engl J Med, 2015 Jun 02; 373(1). PMID: 26027431    Free PMC article.
Highly Cited.
Pembrolizumab versus investigator-choice chemotherapy for ipilimumab-refractory melanoma (KEYNOTE-002): a randomised, controlled, phase 2 trial.
Antoni Ribas, Igor Puzanov, +33 authors, Adil Daud.
Lancet Oncol, 2015 Jun 28; 16(8). PMID: 26115796    Free PMC article.
Highly Cited.
Targeting CD38 with Daratumumab Monotherapy in Multiple Myeloma.
Henk M Lokhorst, Torben Plesner, +18 authors, Paul G Richardson.
N Engl J Med, 2015 Aug 27; 373(13). PMID: 26308596
Highly Cited.
FcγRs Modulate the Anti-tumor Activity of Antibodies Targeting the PD-1/PD-L1 Axis.
Rony Dahan, Emanuela Sega, +3 authors, Jeffrey V Ravetch.
Cancer Cell, 2015 Sep 17; 28(3). PMID: 26373277
Highly Cited.
Development and Characterization of Monoclonal Antibodies Specific for Mouse and Human Fcγ Receptors.
Alison L Tutt, Sonya James, +24 authors, Mark S Cragg.
J Immunol, 2015 Oct 30; 195(11). PMID: 26512139
Combination OX40 agonism/CTLA-4 blockade with HER2 vaccination reverses T-cell anergy and promotes survival in tumor-bearing mice.
Stefanie N Linch, Melissa J Kasiewicz, +3 authors, William L Redmond.
Proc Natl Acad Sci U S A, 2016 Jan 06; 113(3). PMID: 26729864    Free PMC article.
Expansion and Activation of CD103(+) Dendritic Cell Progenitors at the Tumor Site Enhances Tumor Responses to Therapeutic PD-L1 and BRAF Inhibition.
Hélène Salmon, Juliana Idoyaga, +19 authors, Miriam Merad.
Immunity, 2016 Apr 21; 44(4). PMID: 27096321    Free PMC article.
Highly Cited.
Coinhibitory Pathways in the B7-CD28 Ligand-Receptor Family.
Frank A Schildberg, Sarah R Klein, Gordon J Freeman, Arlene H Sharpe.
Immunity, 2016 May 19; 44(5). PMID: 27192563    Free PMC article.
Highly Cited. Review.
Therapeutic Activity of Agonistic, Human Anti-CD40 Monoclonal Antibodies Requires Selective FcγR Engagement.
Rony Dahan, Bryan C Barnhart, +3 authors, Jeffrey V Ravetch.
Cancer Cell, 2016 Jun 07; 29(6). PMID: 27265505    Free PMC article.
Highly Cited.
The role of myeloid cells in cancer therapies.
Camilla Engblom, Christina Pfirschke, Mikael J Pittet.
Nat Rev Cancer, 2016 Jun 25; 16(7). PMID: 27339708
Highly Cited. Review.
Primary, Adaptive, and Acquired Resistance to Cancer Immunotherapy.
Padmanee Sharma, Siwen Hu-Lieskovan, Jennifer A Wargo, Antoni Ribas.
Cell, 2017 Feb 12; 168(4). PMID: 28187290    Free PMC article.
Highly Cited. Review.
Fc-Optimized Anti-CD25 Depletes Tumor-Infiltrating Regulatory T Cells and Synergizes with PD-1 Blockade to Eradicate Established Tumors.
Frederick Arce Vargas, Andrew J S Furness, +29 authors, Sergio A Quezada.
Immunity, 2017 Apr 16; 46(4). PMID: 28410988    Free PMC article.
Highly Cited.
In vivo imaging reveals a tumor-associated macrophage-mediated resistance pathway in anti-PD-1 therapy.
Sean P Arlauckas, Christopher S Garris, +9 authors, Mikael J Pittet.
Sci Transl Med, 2017 May 12; 9(389). PMID: 28490665    Free PMC article.
Highly Cited.
Timing of PD-1 Blockade Is Critical to Effective Combination Immunotherapy with Anti-OX40.
David J Messenheimer, Shawn M Jensen, +6 authors, Bernard A Fox.
Clin Cancer Res, 2017 Sep 01; 23(20). PMID: 28855348    Free PMC article.
Highly Cited.
Fc Effector Function Contributes to the Activity of Human Anti-CTLA-4 Antibodies.
Frederick Arce Vargas, Andrew J S Furness, +32 authors, Sergio A Quezada.
Cancer Cell, 2018 Mar 27; 33(4). PMID: 29576375    Free PMC article.
Highly Cited.
The "less-is-more" in therapeutic antibodies: Afucosylated anti-cancer antibodies with enhanced antibody-dependent cellular cytotoxicity.
Natasha A Pereira, Kah Fai Chan, Pao Chun Lin, Zhiwei Song.
MAbs, 2018 May 08; 10(5). PMID: 29733746    Free PMC article.
Review.
Antibodies to Costimulatory Receptor 4-1BB Enhance Anti-tumor Immunity via T Regulatory Cell Depletion and Promotion of CD8 T Cell Effector Function.
Sarah L Buchan, Lang Dou, +26 authors, Stephen A Beers.
Immunity, 2018 Nov 18; 49(5). PMID: 30446386
Monoclonal antibodies against the 4-1BB T-cell activation molecule eradicate established tumors.
I Melero, W W Shuford, +5 authors, L Chen.
Nat Med, 1997 Jun 01; 3(6). PMID: 9176498
Highly Cited.
Fc gamma RIIIB gene duplication: evidence for presence and expression of three distinct Fc gamma RIIIB genes in NA(1+,2+)SH(+) individuals.
H R Koene, M Kleijer, +2 authors, A E Von dem Borne.
Blood, 1998 Jan 15; 91(2). PMID: 9427724
Fcgamma receptor-mediated induction of dendritic cell maturation and major histocompatibility complex class I-restricted antigen presentation after immune complex internalization.
A Regnault, D Lankar, +8 authors, S Amigorena.
J Exp Med, 1999 Jan 20; 189(2). PMID: 9892619    Free PMC article.
Highly Cited.
There Is (Scientific) Strength in Numbers: A Comprehensive Quantitation of Fc Gamma Receptor Numbers on Human and Murine Peripheral Blood Leukocytes.
Christina Kerntke, Falk Nimmerjahn, Markus Biburger.
Front Immunol, 2020 Mar 03; 11. PMID: 32117269    Free PMC article.
Reprogramming the Constant Region of Immunoglobulin G Subclasses for Enhanced Therapeutic Potency against Cancer.
Tae Hyun Kang, Sang Taek Jung.
Biomolecules, 2020 Mar 04; 10(3). PMID: 32121592    Free PMC article.
Review.
FcγRIIB engagement drives agonistic activity of Fc-engineered αOX40 antibody to stimulate human tumor-infiltrating T cells.
Lucia Campos Carrascosa, Adriaan A van Beek, +19 authors, Jaap Kwekkeboom.
J Immunother Cancer, 2020 Sep 10; 8(2). PMID: 32900860    Free PMC article.
Phage Display Derived Monoclonal Antibodies: From Bench to Bedside.
Mohamed A Alfaleh, Hashem O Alsaab, +4 authors, Anwar M Hashem.
Front Immunol, 2020 Sep 29; 11. PMID: 32983137    Free PMC article.
Review.
RNA-biology ruling cancer progression? Focus on 3'UTRs and splicing.
Ayse Elif Erson-Bensan.
Cancer Metastasis Rev, 2020 May 04; 39(3). PMID: 32361913
Review.
The Current Landscape of Antibody-based Therapies in Solid Malignancies.
Ashu Shah, Sanchita Rauth, +6 authors, Surinder K Batra.
Theranostics, 2021 Jan 05; 11(3). PMID: 33391547    Free PMC article.
Review.
Tumor-infiltrating CD8+ T cell antitumor efficacy and exhaustion: molecular insights.
Sandeep Kumar, Sunil Kumar Singh, Basabi Rana, Ajay Rana.
Drug Discov Today, 2021 Jan 16; 26(4). PMID: 33450394    Free PMC article.
Review.
The Role of Fc Receptors on the Effectiveness of Therapeutic Monoclonal Antibodies.
Patricia Gogesch, Simone Dudek, +2 authors, Martina Anzaghe.
Int J Mol Sci, 2021 Aug 28; 22(16). PMID: 34445651    Free PMC article.
Review.
Cellular immune responses in the pathophysiology of preeclampsia.
Derek Miller, Kenichiro Motomura, +4 authors, Nardhy Gomez-Lopez.
J Leukoc Biol, 2021 Apr 14; 111(1). PMID: 33847419    Free PMC article.
Review.
Remodeling the Tumor Myeloid Landscape to Enhance Antitumor Antibody Immunotherapies.
Khiyam Hussain, Mark S Cragg, Stephen A Beers.
Cancers (Basel), 2021 Oct 14; 13(19). PMID: 34638388    Free PMC article.
Review.
Anti-PD-L1 Therapy Does Not Improve Survival in a Murine Model of Lethal Staphylococcus aureus Pneumonia.
Colleen S Curran, Lindsay M Busch, +4 authors, Parizad Torabi-Parizi.
J Infect Dis, 2021 May 20; 224(12). PMID: 34009385    Free PMC article.
Systematic Review.
Nanomedicines in B cell-targeting therapies.
Jiawei Wang, Jiyuan Yang, Jindřich Kopeček.
Acta Biomater, 2021 Oct 24; 137. PMID: 34687954    Free PMC article.
Review.
Role of Fcγ receptors in HER2-targeted breast cancer therapy.
Antonino Musolino, William J Gradishar, +4 authors, Mark D Pegram.
J Immunother Cancer, 2022 Jan 08; 10(1). PMID: 34992090    Free PMC article.
Review.
HIF activation enhances FcγRIIb expression on mononuclear phagocytes impeding tumor targeting antibody immunotherapy.
Khiyam Hussain, Rena Liu, +28 authors, Mark S Cragg.
J Exp Clin Cancer Res, 2022 Apr 09; 41(1). PMID: 35392965    Free PMC article.