Skip to main content
SpringerLink
Log in

FcγRIIB as a Key Determinant of Agonistic Antibody Efficacy

  • Chapter
  • First Online:
Fc Receptors

Part of the book series: Current Topics in Microbiology and Immunology ((CT MICROBIOLOGY,volume 382))

Abstract

Fc gamma Receptor (FcγR) IIB (CD32B) is an immunoreceptor tyrosine inhibitory motif (ITIM)-bearing Fc receptor that is involved in abrogating the signalling and function delivered from other receptors; archetypally those arising from other, activatory, FcγR and from the B cell receptor (BCR) for antigen. In the context of immunotherapy, it has convincingly been shown to limit a variety of clinically important therapeutic monoclonal antibodies (mAb) such as rituximab and trastuzumab in preclinical models. However, recent exploration of so-called immunomodulatory mAb, for example agonist mAb directed against various members of the TNFR super-family, has cast new light on the ability of FcγRIIB to regulate immune responses and immunotherapy. These data, accumulated by several independent groups, have shown the seemingly paradoxical ability of FcγRIIB to augment or even be absolutely required for the activity of this class of mAb. In this review we highlight the key role of FcγRIIB in regulating agonistic mAb, detail the likely mechanism of action and propose new ways in which this information may be exploited therapeutically.

Conflict statement: Prof Cragg serves as a consultant for Bioinvent International and has previously served as an ad hoc consultant for Roche.

All authors contributed equally to this study.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 149.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Hardcover Book
USD 199.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Abbreviations

FcγR:

Fc gamma receptor

mAb:

Monoclonal antibody

References

  • Ashkenazi A (2002) Targeting death and decoy receptors of the tumour-necrosis factor superfamily. Nat Rev Cancer 2:420–430

    Article  PubMed  CAS  Google Scholar 

  • Banchereau J, de Paoli P, Valle A, Garcia E, Rousset F (1991) Long-term human B cell lines dependent on interleukin-4 and antibody to CD40. Science 251:70–72

    Article  PubMed  CAS  Google Scholar 

  • Beatty GL, Chiorean EG, Fishman MP, Saboury B, Teitelbaum UR, Sun W et al (2011) CD40 agonists alter tumor stroma and show efficacy against pancreatic carcinoma in mice and humans. Science 331:1612–1616

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  • Beers SA, French RR, Chan CH, Lim SH, Jarrett TC, Vidal RM et al (2010) Antigenic modulation limits the efficacy of anti-CD20 antibodies: implications for antibody selection. Blood 115:5191–5201

    Article  PubMed  CAS  Google Scholar 

  • Bolland S, Pearse RN, Kurosaki T, Ravetch JV (1998) SHIP modulates immune receptor responses by regulating membrane association of Btk. Immunity 8:509–516

    Article  PubMed  CAS  Google Scholar 

  • Brahmer JR, Tykodi SS, Chow LQ, Hwu WJ, Topalian SL, Hwu P et al (2012) Safety and activity of anti-PD-L1 antibody in patients with advanced cancer. N Engl J Med 366:2455–2465

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  • Bruhns P, Iannascoli B, England P, Mancardi DA, Fernandez N, Jorieux S et al (2009) Specificity and affinity of human Fcgamma receptors and their polymorphic variants for human IgG subclasses. Blood 113:3716–3725

    Article  PubMed  CAS  Google Scholar 

  • Bulliard Y, Jolicoeur R, Windman M, Rue SM, Ettenberg S, Knee DA et al (2013) Activating Fc gamma receptors contribute to the antitumor activities of immunoregulatory receptor-targeting antibodies. J Exp Med 210:1685–1693

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  • Burris H, Ansell S, Nemunaitis J, Weiss G, Sikic B, Northfelt D, Pilja L, Davis T, Yellin M, Keler T, Bullock T (2013) A phase I study of an agonist anti-CD27 human antibody (CDX-1127) in patients with advanced hematologic malignancies or solid tumors. poster; society for immunotherapy of cancer 28th annual meeting national harbor, MD, USA, 8–10 November 2013

    Google Scholar 

  • Chuntharapai A, Dodge K, Grimmer K, Schroeder K, Marsters SA, Koeppen H et al (2001) Isotype-dependent inhibition of tumor growth in vivo by monoclonal antibodies to death receptor 4. J Immunol 166:4891–4898

    Article  PubMed  CAS  Google Scholar 

  • Clark EA, Ledbetter JA (1986) Activation of human B cells mediated through two distinct cell surface differentiation antigens, Bp35 and Bp50. Proc Natl Acad Sci U S A 83:4494–4498

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  • Clynes RA, Towers TL, Presta LG, Ravetch JV (2000) Inhibitory Fc receptors modulate in vivo cytoxicity against tumor targets. Nat Med 6:443–446

    Article  PubMed  CAS  Google Scholar 

  • Cragg MS, Walshe CA, Ivanov AO, Glennie MJ (2005) The biology of CD20 and its potential as a target for mAb therapy. Curr Dir Autoimmun 8:140–174

    Article  PubMed  CAS  Google Scholar 

  • Daëron M, Lesourne R (2006) Negative signaling in Fc receptor complexes. Adv Immunol 89:39–86

    Google Scholar 

  • Daeron M, Latour S, Malbec O, Espinosa E, Pina P, Pasmans S et al (1995) The same tyrosine-based inhibition motif, in the intracytoplasmic domain of Fc gamma RIIB, regulates negatively BCR-, TCR-, and FcR-dependent cell activation. Immunity 3:635–646

    Article  PubMed  CAS  Google Scholar 

  • de Haij S, Jansen JH, Boross P, Beurskens FJ, Bakema JE, Bos DL et al (2010) In vivo cytotoxicity of type I CD20 antibodies critically depends on Fc receptor ITAM signaling. Cancer Res 70:3209–3217

    Article  PubMed  Google Scholar 

  • Desai DD, Harbers SO, Flores M, Colonna L, Downie MP, Bergtold A et al (2007) Fc{gamma} receptor IIB on dendritic cells enforces peripheral tolerance by inhibiting effector T cell responses. J Immunol 178:6217–6226

    Article  PubMed  CAS  Google Scholar 

  • Dullforce P, Sutton DC, Heath AW (1998) Enhancement of T cell-independent immune responses in vivo by CD40 antibodies. Nat Med 4:88–91

    Article  PubMed  CAS  Google Scholar 

  • Eliopoulos AG, Young LS (2004) The role of the CD40 pathway in the pathogenesis and treatment of cancer. Curr Opin Pharmacol 4:360–367

    Article  PubMed  CAS  Google Scholar 

  • Enyedy EJ, Mitchell JP, Nambiar MP, Tsokos GC (2001) Defective FcgammaRIIb1 signaling contributes to enhanced calcium response in B cells from patients with systemic lupus erythematosus. Clin Immunol 101:130–135

    Article  PubMed  CAS  Google Scholar 

  • Ferrara C, Stuart F, Sondermann P, Brunker P, Umana P (2006) The carbohydrate at FcgammaRIIIa Asn-162. An element required for high affinity binding to non-fucosylated IgG glycoforms. J Biol Chem 281:5032–5036

    Article  PubMed  CAS  Google Scholar 

  • Flores M, Desai DD, Downie M, Liang B, Reilly MP, McKenzie SE et al (2009) Dominant expression of the inhibitory FcgammaRIIB prevents antigen presentation by murine plasmacytoid dendritic cells. J Immunol 183:7129–7139

    Article  PubMed  CAS  Google Scholar 

  • Fong DC, Brauweiler A, Minskoff SA, Bruhns P, Tamir I, Mellman I et al (2000) Mutational analysis reveals multiple distinct sites within Fc gamma receptor IIB that function in inhibitory signaling. J Immunol 165:4453–4462

    Article  PubMed  CAS  Google Scholar 

  • French RR, Chan HT, Tutt AL, Glennie MJ (1999) CD40 antibody evokes a cytotoxic T-cell response that eradicates lymphoma and bypasses T-cell help. Nat Med 5:548–553

    Article  PubMed  CAS  Google Scholar 

  • Galy AH, Spits H (1992) CD40 is functionally expressed on human thymic epithelial cells. J Immunol 149:775–782

    PubMed  CAS  Google Scholar 

  • Gieffers C, Kluge M, Merz C, Sykora J, Thiemann M, Schaal R et al (2013) APG350 induces superior clustering of TRAIL-Receptors and shows therapeutic anti-tumor efficacy independent of cross-linking via Fcgamma-Receptors. Mol Cancer Ther 12(12):2735–2747

    Google Scholar 

  • Golay J, Da Roit F, Bologna L, Ferrara C, Leusen JH, Rambaldi A et al (2013) Glycoengineered CD20 antibody obinutuzumab activates neutrophils and mediates phagocytosis through CD16B more efficiently than rituximab. Blood 122:3482–3491

    Article  PubMed  CAS  Google Scholar 

  • Gong Q, Ou Q, Ye S, Lee WP, Cornelius J, Diehl L et al (2005) Importance of cellular microenvironment and circulatory dynamics in B cell immunotherapy. J Immunol 174:817–826

    Article  PubMed  CAS  Google Scholar 

  • Green SK, Karlsson MC, Ravetch JV, Kerbel RS (2002) Disruption of cell-cell adhesion enhances antibody-dependent cellular cytotoxicity: implications for antibody-based therapeutics of cancer. Cancer Res 62:6891–6900

    PubMed  CAS  Google Scholar 

  • Ha SJ, Mueller SN, Wherry EJ, Barber DL, Aubert RD, Sharpe AH et al (2008) Enhancing therapeutic vaccination by blocking PD-1-mediated inhibitory signals during chronic infection. J Exp Med 205:543–555

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  • Hamaguchi Y, Xiu Y, Komura K, Nimmerjahn F, Tedder TF (2006) Antibody isotype-specific engagement of Fcgamma receptors regulates B lymphocyte depletion during CD20 immunotherapy. J Exp Med 203:743–753

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  • Hart DN, McKenzie JL (1988) Isolation and characterization of human tonsil dendritic cells. J Exp Med 168:157–170

    Article  PubMed  CAS  Google Scholar 

  • Haynes NM, Hawkins ED, Li M, McLaughlin NM, Hammerling GJ, Schwendener R et al (2010) CD11c + dendritic cells and B cells contribute to the tumoricidal activity of anti-DR5 antibody therapy in established tumors. J Immunol 185:532–541

    Article  PubMed  CAS  Google Scholar 

  • He LZ, Prostak N, Thomas LJ, Vitale L, Weidlick J, Crocker A et al (2013) Agonist anti-human CD27 monoclonal antibody induces T cell activation and tumor immunity in human CD27-transgenic mice. J Immunol 191:4174–4183

    Article  PubMed  CAS  Google Scholar 

  • Hodi FS, O’Day SJ, McDermott DF, Weber RW, Sosman JA, Haanen JB et al (2010) Improved survival with ipilimumab in patients with metastatic melanoma. N Engl J Med 363:711–723

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  • Jonsson F, Mancardi DA, Albanesi M, Bruhns P (2013) Neutrophils in local and systemic antibody-dependent inflammatory and anaphylactic reactions. J Leukoc Biol 94:643–656

    Article  PubMed  CAS  Google Scholar 

  • Kaneko Y, Nimmerjahn F, Ravetch JV (2006) Anti-inflammatory activity of immunoglobulin G resulting from Fc sialylation. Science 313:670–673

    Article  PubMed  CAS  Google Scholar 

  • Kellner C, Derer S, Valerius T, Peipp M (2013) Boosting ADCC and CDC activity by Fc engineering and evaluation of antibody effector functions. Methods 65(1):105–113

    Google Scholar 

  • Law CL, Gordon KA, Collier J, Klussman K, McEarchern JA, Cerveny CG et al (2005) Preclinical antilymphoma activity of a humanized anti-CD40 monoclonal antibody, SGN-40. Cancer Res 65:8331–8338

    Article  PubMed  CAS  Google Scholar 

  • Lee CC, Cragg M, Glennie MJ, Johnson P (2012) Novel monoclonal antibody approaches to cancer immunotherapy. Br J Clin Pharmacol

    Google Scholar 

  • Li F, Ravetch JV (2013) Antitumor activities of agonistic anti-TNFR antibodies require differential FcgammaRIIB coengagement in vivo. Proc Natl Acad Sci U S A 110(48):19501–19506

    Google Scholar 

  • Li F, Ravetch JV (2012) Apoptotic and antitumor activity of death receptor antibodies require inhibitory Fcgamma receptor engagement. Proc Natl Acad Sci U S A 109:10966–10971

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  • Li F, Ravetch JV (2011) Inhibitory Fcgamma receptor engagement drives adjuvant and anti-tumor activities of agonistic CD40 antibodies. Science 333:1030–1034

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  • Li X, Wu J, Carter RH, Edberg JC, Su K, Cooper GS et al (2003) A novel polymorphism in the Fcgamma receptor IIB (CD32B) transmembrane region alters receptor signaling. Arthritis Rheum 48:3242–3252

    Article  PubMed  CAS  Google Scholar 

  • Lim SH, Beers SA, French RR, Johnson PW, Glennie MJ, Cragg MS (2010) Anti-CD20 monoclonal antibodies: historical and future perspectives. Haematologica 95:135–143

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  • Lim SH, Vaughan AT, Ashton-Key M, Williams EL, Dixon SV, Chan CH et al (2011) Fc gamma receptor IIb on target B cells promotes rituximab internalization and reduces clinical efficacy. Blood 118(9):2530–2340

    Google Scholar 

  • Liu YJ, Joshua DE, Williams GT, Smith CA, Gordon J, MacLennan IC (1989) Mechanism of antigen-driven selection in germinal centres. Nature 342:929–931

    Article  PubMed  CAS  Google Scholar 

  • Mimoto F, Katada H, Kadono S, Igawa T, Kuramochi T, Muraoka M et al (2013) Engineered antibody Fc variant with selectively enhanced FcgammaRIIb binding over both FcgammaRIIa(R131) and FcgammaRIIa(H131). Protein Eng Des Sel 26:589–598

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  • Minard-Colin V, Xiu Y, Poe JC, Horikawa M, Magro CM, Hamaguchi Y et al (2008) Lymphoma depletion during CD20 immunotherapy in mice is mediated by macrophage FcgammaRI, FcgammaRIII, and FcgammaRIV. Blood 112:1205–1213

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  • Mossner E, Brunker P, Moser S, Puntener U, Schmidt C, Herter S et al (2010) Increasing the efficacy of CD20 antibody therapy through the engineering of a new type II anti-CD20 antibody with enhanced direct and immune effector cell-mediated B-cell cytotoxicity. Blood 115:4393–4402

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  • Muta T, Kurosaki T, Misulovin Z, Sanchez M, Nussenzweig MC, Ravetch JV (1994) A 13-amino-acid motif in the cytoplasmic domain of Fc gamma RIIB modulates B-cell receptor signalling. Nature 369:340

    PubMed  CAS  Google Scholar 

  • Nimmerjahn F, Bruhns P, Horiuchi K, Ravetch JV (2005) FcgammaRIV: a novel FcR with distinct IgG subclass specificity. Immunity 23:41–51

    Article  PubMed  CAS  Google Scholar 

  • Nimmerjahn F, Ravetch JV (2007a) Antibodies, Fc receptors and cancer. Curr Opin Immunol 19:239–245

    Article  PubMed  CAS  Google Scholar 

  • Nimmerjahn F, Ravetch JV (2005) Divergent immunoglobulin g subclass activity through selective Fc receptor binding. Science 310:1510–1512

    Article  PubMed  CAS  Google Scholar 

  • Nimmerjahn F, Ravetch JV (2007b) Fc-receptors as regulators of immunity. Adv Immunol 96:179–204

    Article  PubMed  CAS  Google Scholar 

  • Nimmerjahn F, Ravetch JV (2006) Fcgamma receptors: old friends and new family members. Immunity 24:19–28

    Article  PubMed  CAS  Google Scholar 

  • Nunes J, Klasen S, Ragueneau M, Pavon C, Couez D, Mawas C et al (1993) CD28 mAbs with distinct binding properties differ in their ability to induce T cell activation: analysis of early and late activation events. Int Immunol 5:311–315

    Article  PubMed  CAS  Google Scholar 

  • Oflazoglu E, Stone IJ, Brown L, Gordon KA, van Rooijen N, Jonas M et al (2009) Macrophages and Fc-receptor interactions contribute to the antitumour activities of the anti-CD40 antibody SGN-40. Br J Cancer 100:113–117

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  • Okada H, Bolland S, Hashimoto A, Kurosaki M, Kabuyama Y, Iino M et al (1998) Role of the inositol phosphatase SHIP in B cell receptor-induced Ca2 + oscillatory response. J Immunol 161:5129–5132

    PubMed  CAS  Google Scholar 

  • Ono M, Bolland S, Tempst P, Ravetch JV (1996) Role of the inositol phosphatase SHIP in negative regulation of the immune system by the receptor Fc(gamma)RIIB. Nature 383:263–266

    Article  PubMed  CAS  Google Scholar 

  • Palmer BE, Neff CP, Lecureux J, Ehler A, Dsouza M, Remling-Mulder L et al (2013) In vivo blockade of the PD-1 receptor suppresses HIV-1 viral loads and improves CD4 + T cell levels in humanized mice. J Immunol 190:211–219

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  • Paulie S, Ehlin-Henriksson B, Mellstedt H, Koho H, Ben-Aissa H, Perlmann P (1985) A p50 surface antigen restricted to human urinary bladder carcinomas and B lymphocytes. Cancer Immunol Immunother 20:23–28

    Article  PubMed  CAS  Google Scholar 

  • Paulie S, Rosen A, Ehlin-Henriksson B, Braesch-Andersen S, Jakobson E, Koho H et al (1989) The human B lymphocyte and carcinoma antigen, CDw40, is a phosphoprotein involved in growth signal transduction. J Immunol 142:590–595

    PubMed  CAS  Google Scholar 

  • Peggs KS, Quezada SA, Chambers CA, Korman AJ, Allison JP (2009) Blockade of CTLA-4 on both effector and regulatory T cell compartments contributes to the antitumor activity of anti-CTLA-4 antibodies. J Exp Med 206:1717–1725

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  • Phillips NE, Parker DC (1983) Fc-dependent inhibition of mouse B cell activation by whole anti-mu antibodies. J Immunol 130:602–606

    PubMed  CAS  Google Scholar 

  • Radstake TR, Franke B, Wenink MH, Nabbe KC, Coenen MJ, Welsing P et al (2006) The functional variant of the inhibitory Fcgamma receptor IIb (CD32B) is associated with the rate of radiologic joint damage and dendritic cell function in rheumatoid arthritis. Arthritis Rheum 54:3828–3837

    Article  PubMed  CAS  Google Scholar 

  • Ravetch JV, Bolland S (2001) IgG Fc receptors. Annu Rev Immunol 19:275–290

    Article  PubMed  CAS  Google Scholar 

  • Reichert JM, Dhimolea E (2012) The future of antibodies as cancer drugs. Drug Discov Today 17:954–63

    Google Scholar 

  • Roberts DJ, Franklin NA, Kingeter LM, Yagita H, Tutt AL, Glennie MJ et al (2010) Control of established melanoma by CD27 stimulation is associated with enhanced effector function and persistence, and reduced PD-1 expression of tumor infiltrating CD8(+) T cells. J Immunother 33:769–779

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  • Roche (2013) FDA approves Roche’s Gazyva (obinutuzumab) for people with previously untreated chronic lymphocytic leukemia (CLL). Press Release. http://www.roche.com/media/media_releases/med-cor-2013-11-01.htm

  • Sato K, Ochi A (1998) Superclustering of B cell receptor and Fc gamma RIIB1 activates Src homology 2-containing protein tyrosine phosphatase-1. J Immunol 161:2716–2722

    PubMed  CAS  Google Scholar 

  • Schriever F, Freedman AS, Freeman G, Messner E, Lee G, Daley J et al (1989) Isolated human follicular dendritic cells display a unique antigenic phenotype. J Exp Med 169:2043–2058

    Article  PubMed  CAS  Google Scholar 

  • Selby MJ, Engelhardt JJ, Quigley M, Henning KA, Chen T, Srinivasan M, Korman AJ (2013) Anti-CTLA-4 Antibodies of IgG2a isotype enhance antitumour activity through reduction of intratumoral regulatory T cells. Cancer Immunol Res 1(1):32–42

    Google Scholar 

  • Simpson TR, Li F, Montalvo-Ortiz W, Sepulveda MA, Bergerhoff K, Arce F et al (2013) Fc-dependent depletion of tumor-infiltrating regulatory T cells co-defines the efficacy of anti-CTLA-4 therapy against melanoma. J Exp Med 210:1695–1710

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  • Takeda K, Yamaguchi N, Akiba H, Kojima Y, Hayakawa Y, Tanner JE et al (2004) Induction of tumor-specific T cell immunity by anti-DR5 antibody therapy. J Exp Med 199:437–448

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  • Topalian SL, Hodi FS, Brahmer JR, Gettinger SN, Smith DC, McDermott DF et al (2012) Safety, activity, and immune correlates of anti-PD-1 antibody in cancer. N Engl J Med 366:2443–2454

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  • Tutt AL, O’Brien L, Hussain A, Crowther GR, French RR, Glennie MJ (2002) T cell immunity to lymphoma following treatment with anti-CD40 monoclonal antibody. J Immunol 168:2720–2728

    Article  PubMed  CAS  Google Scholar 

  • Uchida J, Hamaguchi Y, Oliver JA, Ravetch JV, Poe JC, Haas KM et al (2004) The innate mononuclear phagocyte network depletes B lymphocytes through Fc receptor-dependent mechanisms during anti-CD20 antibody immunotherapy. J Exp Med 199:1659–1669

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  • Vaughan AT, Iriyama C, Beers SA, Chan CHT, Lim SH, Williams EL et al (2013) Inhibitory FcγRIIb (CD32b) becomes activated by therapeutic mAb in both cis and trans and drives internalization according to antibody specificity. Blood 123(5): 669–677

    Google Scholar 

  • Vitale LA, He LZ, Thomas LJ, Widger J, Weidlick J, Crocker A et al (2012) Development of a human monoclonal antibody for potential therapy of CD27-expressing lymphoma and leukemia. Clin Cancer Res 18:3812–3821

    Article  PubMed  CAS  Google Scholar 

  • Vonderheide RH, Glennie MJ (2013) Agonistic CD40 antibodies and cancer therapy. Clin Cancer Res 19:1035–43

    Google Scholar 

  • Walshe CA, Beers SA, French RR, Chan CH, Johnson PW, Packham GK et al (2008) Induction of cytosolic calcium flux by CD20 is dependent upon B Cell antigen receptor signaling. J Biol Chem 283:16971–16984

    Article  PubMed  CAS  Google Scholar 

  • White AL, Chan HT, French RR, Beers SA, Cragg MS, Johnson PW et al (2013) FcgammaRIIB controls the potency of agonistic anti-TNFR mAbs. Cancer Immunol Immunother 62:941–948

    Article  PubMed  CAS  Google Scholar 

  • White AL, Chan HTC, Roghanian A, French RR, Mockridge CI, Tutt AL et al (2011) Interaction with Fc gamma RIIB is critical for the agonistic activity of anti-CD40 monoclonal antibody. J Immunol 187:1754–1763

    Article  PubMed  CAS  Google Scholar 

  • White AL, Dou L, Chan HTC, Field VL, Mockridge CI, Moss K, Williams E, Butts C, Al-Shamkhani A, Cragg MS, Verbeek SJ, Johnson P, Glennie MJ, Beers SA (2014) FcR dependence of agonistic CD40 antibody is related to anatomical location and can be overcome by antibody multimerisation. J Immunology (in press)

    Google Scholar 

  • Williams EL, Tutt AL, Beers SA, French RR, Chan CH, Cox KL et al (2013) Immunotherapy targeting inhibitory Fcgamma receptor IIB (CD32b) in the mouse is limited by monoclonal antibody consumption and receptor internalization. J Immunol 191:4130–4140

    Article  PubMed  CAS  Google Scholar 

  • Williams EL, Tutt AL, French RR, Chan HT, Lau B, Penfold CA et al (2012) Development and characterisation of monoclonal antibodies specific for the murine inhibitory FcgammaRIIB (CD32B). Eur J Immunol 42:2109–2120

    Article  PubMed  CAS  Google Scholar 

  • Wilson NS, Yang B, Yang A, Loeser S, Marsters S, Lawrence D et al (2011) An Fcgamma receptor-dependent mechanism drives antibody-mediated target-receptor signaling in cancer cells. Cancer Cell 19:101–113

    Article  PubMed  CAS  Google Scholar 

  • Wolchok JD, Kluger H, Callahan MK, Postow MA, Rizvi NA, Lesokhin AM et al (2013) Nivolumab plus ipilimumab in advanced melanoma. N Engl J Med 369:122–133

    Article  PubMed  CAS  Google Scholar 

  • Xu Y, Szalai AJ, Zhou T, Zinn KR, Chaudhuri TR, Li X et al (2003) Fc gamma Rs modulate cytotoxicity of anti-Fas antibodies: implications for agonistic antibody-based therapeutics. J Immunol 171:562–568

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgments

The authors would like to thank all of the members of the Antibody and Vaccine Group, past and present, and in particular the members of the CD20, CD40 and FcγR teams. We also apologise to those authors whose work has not been cited in this review due to space limitations.

Author information

Authors and Affiliations

  1. Cancer Sciences Unit, Antibody and Vaccine Group (MP88), Faculty of Medicine, Southampton University, Tremona Road, Southampton, SO16 6YD, UK

    Ann L. White, Stephen A. Beers & Mark S. Cragg

Authors
  1. Ann L. White
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Stephen A. Beers
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Mark S. Cragg
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Mark S. Cragg .

Editor information

Editors and Affiliations

  1. Institut Pasteur, Paris, France

    Marc Daeron

  2. Department of Biology, Institute of Genetics, University of Erlangen-Nürnberg, Erlangen, Germany

    Falk Nimmerjahn

Rights and permissions

Reprints and permissions

Copyright information

© 2014 Springer International Publishing Switzerland

About this chapter

Cite this chapter

White, A.L., Beers, S.A., Cragg, M.S. (2014). FcγRIIB as a Key Determinant of Agonistic Antibody Efficacy. In: Daeron, M., Nimmerjahn, F. (eds) Fc Receptors. Current Topics in Microbiology and Immunology, vol 382. Springer, Cham. https://doi.org/10.1007/978-3-319-07911-0_16

Download citation

Publish with us

Policies and ethics

Search

Navigation