Abstract
Targeted therapies like treatment with monoclonal antibodies (mAbs) have entered the arsenal of modern anticancer drugs. mAbs combine specificity with multiple effector functions that can lead to reduction of tumour burden. Direct mechanisms of action, including induction of apoptosis or growth inhibition, depend on the biology of the target antigen. Fc tails of mAbs have furthermore the potential to initiate complement-dependent lysis as well as immune effector cell-mediated tumour cell killing via binding to Fc receptors. Natural killer cells can induce apoptosis via antibody-dependent cellular cytotoxicity (ADCC), whereas macrophages are able to phagocytose mAb-opsonized tumour cells (antibody-dependent cellular phagocytosis; ADCP). Finally, neutrophils can induce non-apoptotic tumour cell death, especially in the presence of immunoglobulin A (IgA) antitumour mAbs. In spite of promising clinical successes in some malignancies, improvement of mAb immunotherapy is required to achieve overall complete remission in cancer patients. New strategies to enhance Fc receptor-mediated mechanisms of action or to overcome the immunosuppressive microenvironment of the tumour in mAb therapy of cancer are therefore currently being explored and will be addressed in this chapter.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
References
Akewanlop C, Watanabe M, Singh B, Walker M, Kufe DW, Hayes DF (2001) Phagocytosis of breast cancer cells mediated by anti-MUC-1 monoclonal antibody, DF3, and its bispecific antibody. Cancer Res 61:4061–4065
Albanesi M, Mancardi DA, Jonsson F, Iannascoli B, Fiette L, di Santo JP, Lowell CA, Bruhns P (2013) Neutrophils mediate antibody-induced antitumor effects in mice. Blood 122:3160–3164
Alduaij W, Illidge TM (2011) The future of anti-CD20 monoclonal antibodies: are we making progress? Blood 117:2993–3001
Amoroso A, Hafsi S, Militello L, Russo AE, Soua Z, Mazzarino MC, Stivala F, Libra M (2011) Understanding rituximab function and resistance: implications for tailored therapy. Front Biosci (Landmark Ed) 16:770–782
Amulic B, Cazalet C, Hayes GL, Metzler KD, Zychlinsky A (2012) Neutrophil function: from mechanisms to disease. Annu Rev Immunol 30:459–489
Arnould L, Gelly M, Penault-Llorca F, Benoit L, Bonnetain F, Migeon C, Cabaret V, Fermeaux V, Bertheau P, Garnier J, Jeannin JF, Coudert B (2006) Trastuzumab-based treatment of HER2-positive breast cancer: an antibody-dependent cellular cytotoxicity mechanism? Br J Cancer 94:259–267
Ashraf SQ, Umana P, Mossner E, Ntouroupi T, Brunker P, Schmidt C, Wilding JL, Mortensen NJ, Bodmer WF (2009) Humanised IgG1 antibody variants targeting membrane-bound carcinoembryonic antigen by antibody-dependent cellular cytotoxicity and phagocytosis. Br J Cancer 101:1758–1768
Bakema JE, Ganzevles SH, Fluitsma DM, Schilham MW, Beelen RH, Valerius T, Lohse S, Glennie MJ, Medema JP, van Egmond M (2011) Targeting FcalphaRI on polymorphonuclear cells induces tumor cell killing through autophagy. J Immunol 187:726–732
Benvenuti S, Sartore-Bianchi A, di Nicolantonio F, Zanon C, Moroni M, Veronese S, Siena S, Bardelli A (2007) Oncogenic activation of the RAS/RAF signalling pathway impairs the response of metastatic colorectal cancers to anti-epidermal growth factor receptor antibody therapies. Cancer Res 67:2643–2648
Bevaart L, Jansen MJ, van Vugt MJ, Verbeek JS, van de Winkel JG, Leusen JH (2006) The high-affinity IgG receptor, FcgammaRI, plays a central role in antibody therapy of experimental melanoma. Cancer Res 66:1261–1264
Beyer T, Lohse S, Berger S, Peipp M, Valerius T, Dechant M (2009) Serum-free production and purification of chimeric IgA antibodies. J Immunol Methods 346:26–37
Bibeau F, Lopez-Crapez E, di Fiore F, Thezenas S, Ychou M, Blanchard F, Lamy A, Penault-Llorca F, Frebourg T, Michel P, Sabourin JC, Boissiere-Michot F (2009) Impact of Fc{gamma}RIIa-Fc{gamma}RIIIa polymorphisms and KRAS mutations on the clinical outcome of patients with metastatic colorectal cancer treated with cetuximab plus irinotecan. J Clin Oncol 27:1122–1129
Bologna L, Gotti E, da Roit F, Intermesoli T, Rambaldi A, Introna M, Golay J (2013) Ofatumumab is more efficient than rituximab in lysing B-chronic lymphocytic leukemia cells in whole blood and in combination with chemotherapy. J Immunol 190:231–239
Bologna L, Gotti E, Manganini M, Rambaldi A, Intermesoli T, Introna M, Golay J (2011) Mechanism of action of type II, glycoengineered, anti-CD20 monoclonal antibody GA101 in B-chronic lymphocytic leukemia whole blood assays in comparison with rituximab and alemtuzumab. J Immunol 186:3762–3769
Boross P, Lohse S, Nederend M, Jansen JH, van Tetering G, Dechant M, Peipp M, Royle L, Liew LP, Boon L, van Rooijen N, Bleeker WK, Parren PW, van de Winkel JG, Valerius T, Leusen JH (2013) IgA EGFR antibodies mediate tumour killing in vivo. EMBO Mol Med 5:1213–1226
Bulliard Y, Jolicoeur R, Windman M, Rue SM, Ettenberg S, Knee DA, Wilson NS, Dranoff G, Brogdon JL (2013) Activating Fc gamma receptors contribute to the antitumor activities of immunoregulatory receptor-targeting antibodies. J Exp Med 210:1685–1693
Chao MP, Alizadeh AA, Tang C, Myklebust JH, Varghese B, Gill S, Jan M, Cha AC, Chan CK, Tan BT, Park CY, Zhao F, Kohrt HE, Malumbres R, Briones J, Gascoyne RD, Lossos IS, Levy R, Weissman IL, Majeti R (2010) Anti-CD47 antibody synergizes with rituximab to promote phagocytosis and eradicate non-Hodgkin lymphoma. Cell 142:699–713
Clynes R, Takechi Y, Moroi Y, Houghton A, Ravetch JV (1998) Fc receptors are required in passive and active immunity to melanoma. Proc Natl Acad Sci USA 95:652–656
Clynes RA, Towers TL, Presta LG, Ravetch JV (2000) Inhibitory Fc receptors modulate in vivo cytotoxicity against tumor targets. Nat Med 6:443–446
Costantini C, Cassatella MA (2011) The defensive alliance between neutrophils and NK cells as a novel arm of innate immunity. J Leukoc Biol 89:221–233
Curnow RT (1997) Clinical experience with CD64-directed immunotherapy. An overview. Cancer Immunol Immunother 45:210–215
de Haij S, Jansen JH, Boross P, Beurskens FJ, Bakema JE, Bos DL, Martens A, Verbeek JS, Parren PW, van de Winkel JG, Leusen JH (2010) In vivo cytotoxicity of type I CD20 antibodies critically depends on Fc receptor ITAM signalling. Cancer Res 70:3209–3217
Deo YM, Sundarapandiyan K, Keler T, Wallace PK, Graziano RF (1998) Bispecific molecules directed to the Fc receptor for IgA (Fc alpha RI, CD89) and tumor antigens efficiently promote cell-mediated cytotoxicity of tumor targets in whole blood. J Immunol 160:1677–1686
Ferrara C, Grau S, Jager C, Sondermann P, Brunker P, Waldhauer I, Hennig M, Ruf A, Rufer AC, Stihle M, Umana P, Benz J (2011) Unique carbohydrate-carbohydrate interactions are required for high affinity binding between FcgammaRIII and antibodies lacking core fucose. Proc Natl Acad Sci USA 108:12669–12674
Francisco JA, Cerveny CG, Meyer DL, Mixan BJ, Klussman K, Chace DF, Rejniak SX, Gordon KA, Deblanc R, Toki BE, Law CL, Doronina SO, Siegall CB, Senter PD, Wahl AF (2003) cAC10-vcMMAE, an anti-CD30-monomethyl auristatin E conjugate with potent and selective antitumor activity. Blood 102:1458–1465
Fridlender ZG, Sun J, Kim S, Kapoor V, Cheng G, Ling L, Worthen GS, Albelda SM (2009) Polarisation of tumor-associated neutrophil phenotype by TGF-beta: “N1” versus “N2” TAN. Cancer Cell 16:183–194
Glennie MJ, French RR, Cragg MS, Taylor RP (2007) Mechanisms of killing by anti-CD20 monoclonal antibodies. Mol Immunol 44:3823–3837
Golay J, da Roit F, Bologna L, Ferrara C, Leusen JH, Rambaldi A, Klein C, Introna M (2013) Glycoengineered CD20 antibody obinutuzumab activates neutrophils and mediates phagocytosis through CD16B more efficiently than rituximab. Blood 122:3482–3491
Grossman WJ, Ley TJ (2004) Granzymes A and B are not expressed in human neutrophils. Blood 104:906-907 (author reply 907–8)
Grugan KD, McCabe FL, Kinder M, Greenplate AR, Harman BC, Ekert JE, van Rooijen N, Anderson GM, Nemeth JA, Strohl WR, Jordan RE, Brezski RJ (2012) Tumor-associated macrophages promote invasion while retaining Fc-dependent antitumor function. J Immunol 189:5457–5466
Gül N, Babes LKS, KorthouwerR, Bögels M, Braster R, Vidarsson G, ten Hagen TLM, Kubes P, van Egmond M (2014) Antibody-dependent phagocytosis by macrophages is a main effector mechanism to prevent development of liver metastases. J Clin Invest 124(2):812–813
Gul N, Bogels M, Grewal S, van der Meer AJ, Rojas LB, Fluitsma DM, van den Tol MP, Hoeben KA, van Marle J, de Vries HE, Beelen RH, van Egmond M (2011) Surgery-induced reactive oxygen species enhance colon carcinoma cell binding by disrupting the liver endothelial cell lining. Gut 60:1076–1086
Hartmann F, Renner C, Jung W, da Costa L, Tembrink S, Held G, Sek A, Konig J, Bauer S, Kloft M, Pfreundschuh M (2001) Anti-CD16/CD30 bispecific antibody treatment for Hodgkin’s disease: role of infusion schedule and costimulation with cytokines. Clin Cancer Res 7:1873–1881
Hatjiharissi E, Xu L, Santos DD, Hunter ZR, Ciccarelli BT, Verselis S, Modica M, Cao Y, Manning RJ, Leleu X, Dimmock EA, Kortsaris A, Mitsiades C, Anderson KC, Fox EA, Treon SP (2007) Increased natural killer cell expression of CD16, augmented binding and ADCC activity to rituximab among individuals expressing the Fc{gamma}RIIIa-158 V/V and V/F polymorphism. Blood 110:2561–2564
Hernandez-Ilizaliturri FJ, Jupudy V, Ostberg J, Oflazoglu E, Huberman A, Repasky E, Czuczman MS (2003) Neutrophils contribute to the biological antitumor activity of rituximab in a non-Hodgkin’s lymphoma severe combined immunodeficiency mouse model. Clin Cancer Res 9:5866–5873
Hochegger K, Eller P, Rosenkranz AR (2004) Granzyme A: an additional weapon of human polymorphonuclear neutrophils (PMNs) in innate immunity? Blood 103:1176
Hodi FS, O’Day SJ, McDermott DF, Weber RW, Sosman JA, Haanen JB, Gonzalez R, Robert C, Schadendorf D, Hassel JC, Akerley W, van den Eertwegh AJ, Lutzky J, Lorigan P, Vaubel JM, Linette GP, Hogg D, Ottensmeier CH, Lebbe C, Peschel C, Quirt I, Clark JI, Wolchok JD, Weber JS, Tian J, Yellin MJ, Nichol GM, Hoos A, Urba WJ (2010) Improved survival with ipilimumab in patients with metastatic melanoma. N Engl J Med 363:711–723
Horikawa M, Minard-Colin V, Matsushita T, Tedder TF (2011) Regulatory B cell production of IL-10 inhibits lymphoma depletion during CD20 immunotherapy in mice. J Clin Invest 121:4268–4280
Horner H, Frank C, Dechant C, Repp R, Glennie M, Herrmann M, Stockmeyer B (2007) Intimate cell conjugate formation and exchange of membrane lipids precede apoptosis induction in target cells during antibody-dependent, granulocyte-mediated cytotoxicity. J Immunol 179:337–345
Hubert P, Heitzmann A, Viel S, Nicolas A, Sastre-Garau X, Oppezzo P, Pritsch O, Osinaga E, Amigorena S (2011) Antibody-dependent cell cytotoxicity synapses form in mice during tumor-specific antibody immunotherapy. Cancer Res 71:5134–5143
Huls G, Heijnen IA, Cuomo E, van der Linden J, Boel E, van de Winkel JG, Logtenberg T (1999) Antitumor immune effector mechanisms recruited by phage display-derived fully human IgG1 and IgA1 monoclonal antibodies. Cancer Res 59:5778–5784
Ishida T, Joh T, Uike N, Yamamoto K, Utsunomiya A, Yoshida S, Saburi Y, Miyamoto T, Takemoto S, Suzushima H, Tsukasaki K, Nosaka K, Fujiwara H, Ishitsuka K, Inagaki H, Ogura M, Akinaga S, Tomonaga M, Tobinai K, Ueda R (2012) Defucosylated anti-CCR4 monoclonal antibody (KW-0761) for relapsed adult T cell leukemia-lymphoma: a multicenter phase II study. J Clin Oncol 30:837–842
Jaeger BN, Donadieu J, Cognet C, Bernat C, Ordonez-Rueda D, Barlogis V, Mahlaoui N, Fenis A, Narni-Mancinelli E, Beaupain B, Bellanne-Chantelot C, Bajenoff M, Malissen B, Malissen M, Vivier E, Ugolini S (2012) Neutrophil depletion impairs natural killer cell maturation, function, and homeostasis. J Exp Med 209:565–580
Kolev M, Towner L, Donev R (2011) Complement in cancer and cancer immunotherapy. Arch Immunol Ther Exp (Warsz) 59:407–419
Launay P, Grossetete B, Arcos-Fajardo M, Gaudin E, Torres SP, Beaudoin L, Patey-Mariaud DE, Serre N, Lehuen A, Monteiro RC (2000) Fcalpha receptor (CD89) mediates the development of immunoglobulin A (IgA) nephropathy (Berger’s disease). Evidence for pathogenic soluble receptor-Iga complexes in patients and CD89 transgenic mice. J Exp Med 191:1999–2009
Lazar GA, Dang W, Karki S, Vafa O, Peng JS, Hyun L, Chan C, Chung HS, Eivazi A, Yoder SC, Vielmetter J, Carmichael DF, Hayes RJ, Dahiyat BI (2006) Engineered antibody Fc variants with enhanced effector function. Proc Natl Acad Sci USA 103:4005–4010
Leek RD, Lewis CE, Whitehouse R, Greenall M, Clarke J, Harris AL (1996) Association of macrophage infiltration with angiogenesis and prognosis in invasive breast carcinoma. Cancer Res 56:4625–4629
Lefebvre ML, Krause SW, Salcedo M, Nardin A (2006) Ex vivo-activated human macrophages kill chronic lymphocytic leukemia cells in the presence of rituximab: mechanism of antibody-dependent cellular cytotoxicity and impact of human serum. J Immunother 29:388–397
Lewis CE, Pollard JW (2006) Distinct role of macrophages in different tumor microenvironments. Cancer Res 66:605–612
Liu Z, Gunasekaran K, Wang W, Razinkov V, Sekirov L, Leng E, Sweet H, Foltz I, Howard M, Rousseau AM, Kozlosky C, Fanslow W, Yan W (2013) Asymmetrical Fc engineering greatly enhances ADCC effector function and stability of the modified antibodies. J Biol Chem
Lohse S, Derer S, Beyer T, Klausz K, Peipp M, Leusen JH, van de Winkel JG, Dechant M, Valerius T (2011) Recombinant dimeric IgA antibodies against the epidermal growth factor receptor mediate effective tumor cell killing. J Immunol 186:3770–3778
Mantovani A, Cassatella MA, Costantini C, Jaillon S (2011) Neutrophils in the activation and regulation of innate and adaptive immunity. Nat Rev Immunol 11:519–531
May C, Sapra P, Gerber HP (2012) Advances in bispecific biotherapeutics for the treatment of cancer. Biochem Pharmacol 84:1105–1112
Megiovanni AM, Sanchez F, Robledo-Sarmiento M, Morel C, Gluckman JC, Boudaly S (2006) Polymorphonuclear neutrophils deliver activation signals and antigenic molecules to dendritic cells: a new link between leukocytes upstream of T lymphocytes. J Leukoc Biol 79:977–988
Metkar SS, Froelich CJ (2004) Human neutrophils lack granzyme A, granzyme B, and perforin. Blood 104:905–906 (author reply 907-8)
Minard-Colin V, Xiu Y, Poe JC, Horikawa M, Magro CM, Hamaguchi Y, Haas KM, Tedder TF (2008) Lymphoma depletion during CD20 immunotherapy in mice is mediated by macrophage FcgammaRI, FcgammaRIII, and FcgammaRIV. Blood 112:1205–1213
Mizushima N, Levine B, Cuervo AM, Klionsky DJ (2008) Autophagy fights disease through cellular self-digestion. Nature 451:1069–1075
Moga E, Canto E, Vidal S, Juarez C, Sierra J, Briones J (2011) Interleukin-15 enhances rituximab-dependent cytotoxicity against chronic lymphocytic leukemia cells and overcomes transforming growth factor beta-mediated immunosuppression. Exp Hematol 39:1064–1071
Montalvao F, Garcia Z, Celli S, Breart B, Deguine J, van Rooijen N, Bousso P (2013) The mechanism of anti-CD20-mediated B cell depletion revealed by intravital imaging. J Clin Invest 123:5098–5103
Mosser DM, Edwards JP (2008) Exploring the full spectrum of macrophage activation. Nat Rev Immunol 8:958–969
Musolino A, Naldi N, Bortesi B, Pezzuolo D, Capelletti M, Missale G, Laccabue D, Zerbini A, Camisa R, Bisagni G, Neri TM, Ardizzoni A (2008) Immunoglobulin G fragment C receptor polymorphisms and clinical efficacy of trastuzumab-based therapy in patients with HER-2/neu-positive metastatic breast cancer. J Clin Oncol 26:1789–1796
Nimmerjahn F, Ravetch JV (2005) Divergent immunoglobulin g subclass activity through selective Fc receptor binding. Science 310:1510–1512
O’Day SJ, Hamid O, Urba WJ (2007) Targeting cytotoxic T-lymphocyte antigen-4 (CTLA-4): a novel strategy for the treatment of melanoma and other malignancies. Cancer 110:2614–2627
Oflazoglu E, Stone IJ, Brown L, Gordon KA, van Rooijen N, Jonas M, Law CL, Grewal IS, Gerber HP (2009) Macrophages and Fc receptor interactions contribute to the antitumor activities of the anti-CD40 antibody SGN-40. Br J Cancer 100:113–117
Oflazoglu E, Stone IJ, Gordon KA, Grewal IS, van Rooijen N, Law CL, Gerber HP (2007) Macrophages contribute to the antitumor activity of the anti-CD30 antibody SGN-30. Blood 110:4370–4372
Otten MA, Bakema JE, Tuk CW, Glennie MJ, Tutt AL, Beelen RH, van de Winkel JG, van Egmond M (2012) Enhanced FcalphaRI-mediated neutrophil migration towards tumor colonies in the presence of endothelial cells. Eur J Immunol 42:1815–1821
Otten MA, Rudolph E, Dechant M, Tuk CW, Reijmers RM, Beelen RH, van de Winkel JG, van Egmond M (2005) Immature neutrophils mediate tumor cell killing via IgA but not IgG Fc receptors. J Immunol 174:5472–5480
Otten MA, van der Bij GJ, Verbeek SJ, Nimmerjahn F, Ravetch JV, Beelen RH, van de Winkel JG, van Egmond M (2008) Experimental antibody therapy of liver metastases reveals functional redundancy between Fc gammaRI and Fc gammaRIV. J Immunol 181:6829–6836
Overdijk MB, Verploegen S, Bleeker WK, Parren PW (2014) Role of IgG Fc Receptors in monoclonal antibody therapy of cancer. Chapter 13, Antibody Fc: Linking Adaptive and Innate Immunity. Elsevier, New York
Overdijk MB, Verploegen S, Ortiz Buijsse A, Vink T, Leusen JH, Bleeker WK, Parren PW (2012) Crosstalk between human IgG isotypes and murine effector cells. J Immunol 189:3430–3438
Pascal V, Laffleur B, Debin A, Cuvillier A, van Egmond M, Drocourt D, Imbertie L, Pangault C, Tarte K, Tiraby G, Cogne M (2012) Anti-CD20 IgA can protect mice against lymphoma development: evaluation of the direct impact of IgA and cytotoxic effector recruitment on CD20 target cells. Haematologica 97:1686–1694
Paz-Ares LG, Gomez-Roca C, Delord JP, Cervantes A, Markman B, Corral J, Soria JC, Berge Y, Roda D, Russell-Yarde F, Hollingsworth S, Baselga J, Umana P, Manenti L, Tabernero J (2011) Phase I pharmacokinetic and pharmacodynamic dose-escalation study of RG7160 (GA201), the first glycoengineered monoclonal antibody against the epidermal growth factor receptor, in patients with advanced solid tumors. J Clin Oncol 29:3783–3790
Pelletier M, Maggi L, Micheletti A, Lazzeri E, Tamassia N, Costantini C, Cosmi L, Lunardi C, Annunziato F, Romagnani S, Cassatella MA (2010) Evidence for a cross-talk between human neutrophils and Th17 cells. Blood 115:335–343
Perini GF, Pro B (2013) Brentuximab vedotin in CD30+ lymphomas. Biol Ther 3:15–23
Racila E, Link BK, Weng WK, Witzig TE, Ansell S, Maurer MJ, Huang J, Dahle C, Halwani A, Levy R, Weiner GJ (2008) A polymorphism in the complement component C1qA correlates with prolonged response following rituximab therapy of follicular lymphoma. Clin Cancer Res 14:6697–6703
Rafiq S, Butchar JP, Cheney C, Mo X, Trotta R, Caligiuri M, Jarjoura D, Tridandapani S, Muthusamy N, Byrd JC (2013) Comparative assessment of clinically utilized CD20-directed antibodies in chronic lymphocytic leukemia cells reveals divergent NK cell, monocyte, and macrophage properties. J Immunol 190:2702–2711
Rahbari NN, Aigner M, Thorlund K, Mollberg N, Motschall E, Jensen K, Diener MK, Buchler MW, Koch M, Weitz J (2010) Meta-analysis shows that detection of circulating tumor cells indicates poor prognosis in patients with colorectal cancer. Gastroenterology 138:1714–1726
Reichert JM, Dhimolea E (2012) The future of antibodies as cancer drugs. Drug Discov Today 17:954–963
Repka T, Chiorean EG, Gay J, Herwig KE, Kohl VK, Yee D, Miller JS (2003) Trastuzumab and interleukin-2 in HER2-positive metastatic breast cancer: a pilot study. Clin Cancer Res 9:2440–2446
Richards JO, Karki S, Lazar GA, Chen H, Dang W, Desjarlais JR (2008) Optimization of antibody binding to FcgammaRIIa enhances macrophage phagocytosis of tumor cells. Mol Cancer Ther 7:2517–2527
Schneider-Merck T, Lammerts van Bueren JJ, Berger S, Rossen K, van Berkel PH, Derer S, Beyer T, Lohse S, Bleeker WK, Peipp M, Parren PW, van de Winkel JG, Valerius T, Dechant M (2010) Human IgG2 antibodies against epidermal growth factor receptor effectively trigger antibody-dependent cellular cytotoxicity but, in contrast to IgG1, only by cells of myeloid lineage. J Immunol 184:512–520
Scott AM, Wolchok JD, Old LJ (2012) Antibody therapy of cancer. Nat Rev Cancer 12:278–287
Sebastian M (2010) Review of catumaxomab in the treatment of malignant ascites. Cancer Manag Res 2:283–286
Sen M, Wankowski DM, Garlie NK, Siebenlist RE, van Epps D, Lefever AV, Lum LG (2001) Use of anti-CD3 x anti-HER2/neu bispecific antibody for redirecting cytotoxicity of activated T cells toward HER2/neu+ tumors. J Hematother Stem Cell Res 10:247–260
Shen S, Kepp O, Kroemer G (2012) The end of autophagic cell death? Autophagy 8:1–3
Shuptrine CW, Surana R, Weiner LM (2012) Monoclonal antibodies for the treatment of cancer. Semin Cancer Biol 22:3–13
Siders WM, Shields J, Garron C, Hu Y, Boutin P, Shankara S, Weber W, Roberts B, Kaplan JM (2010) Involvement of neutrophils and natural killer cells in the anti-tumor activity of alemtuzumab in xenograft tumor models. Leuk Lymphoma 51:1293–1304
Sievers EL, Senter PD (2013) Antibody-drug conjugates in cancer therapy. Annu Rev Med 64:15–29
Simpson TR, Li F, Montalvo-Ortiz W, Sepulveda MA, Bergerhoff K, Arce F, Roddie C, Henry JY, Yagita H, Wolchok JD, Peggs KS, Ravetch JV, Allison JP, Quezada SA (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
Sliwkowski MX, Mellman I (2013) Antibody therapeutics in cancer. Science 341:1192–1198
Sondermann P, Huber R, Oosthuizen V, Jacob U (2000) The 3.2-A crystal structure of the human IgG1 Fc fragment-Fc gammaRIII complex. Nature 406:267–273
Srivastava S, Pelloso D, Feng H, Voiles L, Lewis D, Haskova Z, Whitacre M, Trulli S, Chen YJ, Toso J, Jonak ZL, Chang HC, Robertson MJ (2013) Effects of interleukin-18 on natural killer cells: costimulation of activation through Fc receptors for immunoglobulin. Cancer Immunol Immunother 62:1073–1082
Stockmeyer B, Beyer T, Neuhuber W, Repp R, Kalden JR, Valerius T, Herrmann M (2003) Polymorphonuclear granulocytes induce antibody-dependent apoptosis in human breast cancer cells. J Immunol 171:5124–5129
Suttmann H, Riemensberger J, Bentien G, Schmaltz D, Stockle M, Jocham D, Bohle A, Brandau S (2006) Neutrophil granulocytes are required for effective Bacillus Calmette-Guerin immunotherapy of bladder cancer and orchestrate local immune responses. Cancer Res 66:8250–8257
Topp MS, Kufer P, Gokbuget N, Goebeler M, Klinger M, Neumann S, Horst HA, Raff T, Viardot A, Schmid M, Stelljes M, Schaich M, Degenhard E, Kohne-Volland R, Bruggemann M, Ottmann O, Pfeifer H, Burmeister T, Nagorsen D, Schmidt M, Lutterbuese R, Reinhardt C, Baeuerle PA, Kneba M, Einsele H, Riethmuller G, Hoelzer D, Zugmaier G, Bargou RC (2011) Targeted therapy with the T-cell-engaging antibody blinatumomab of chemotherapy-refractory minimal residual disease in B-lineage acute lymphoblastic leukemia patients results in high response rate and prolonged leukemia-free survival. J Clin Oncol 29:2493–2498
Uchida J, Hamaguchi Y, Oliver JA, Ravetch JV, Poe JC, Haas KM, Tedder TF (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
Valerius T, Stockmeyer B, van Spriel AB, Graziano RF, Van den Herik-Oudijk IE, Repp R, Deo YM, Lund J, Kalden JR, Gramatzki M, van de Winkel JG (1997) FcalphaRI (CD89) as a novel trigger molecule for bispecific antibody therapy. Blood 90:4485–4492
van der Bij GJ, Bogels M, Otten MA, Oosterling SJ, Kuppen PJ, Meijer S, Beelen RH, van Egmond M (2010) Experimentally induced liver metastases from colorectal cancer can be prevented by mononuclear phagocyte-mediated monoclonal antibody therapy. J Hepatol 53:677–685
van der Bij GJ, Oosterling SJ, Bogels M, Bhoelan F, Fluitsma DM, Beelen RH, Meijer S, van Egmond M (2008) Blocking alpha2 integrins on rat CC531s colon carcinoma cells prevents operation-induced augmentation of liver metastases outgrowth. Hepatology 47:532–543
van der Steen L, Tuk CW, Bakema JE, Kooij G, Reijerkerk A, Vidarsson G, Bouma G, Kraal G, de Vries HE, Beelen RH, van Egmond M (2009) Immunoglobulin A: Fc(alpha)RI interactions induce neutrophil migration through release of leukotriene B4. Gastroenterology 137(2018–29):e1–e3
van Egmond M, Bakema JE (2013) Neutrophils as effector cells for antibody-based immunotherapy of cancer. Semin Cancer Biol 23:190–199
van Egmond M, van Vuuren AJ, Morton HC, van Spriel AB, Shen L, Hofhuis FM, Saito T, Mayadas TN, Verbeek JS, van de Winkel JG (1999) Human immunoglobulin A receptor (FcalphaRI, CD89) function in transgenic mice requires both FcR gamma chain and CR3 (CD11b/CD18). Blood 93:4387–4394
van Gisbergen KP, Geijtenbeek TB, van Kooyk Y (2005a) Close encounters of neutrophils and DCs. Trends Immunol 26:626–631
van Gisbergen KP, Sanchez-Hernandez M, Geijtenbeek TB, van Kooyk Y (2005b) Neutrophils mediate immune modulation of dendritic cells through glycosylation-dependent interactions between Mac-1 and DC-SIGN. J Exp Med 201:1281–1292
van Loon K, Venook AP (2011) Adjuvant treatment of colon cancer: what is next? Curr Opin Oncol 23:403–409
van Spriel AB, van Ojik HH, Bakker A, Jansen MJ, van de Winkel JG (2003) Mac-1 (CD11b/CD18) is crucial for effective Fc receptor-mediated immunity to melanoma. Blood 101:253–258
Wagner C, Iking-Konert C, Denefleh B, Stegmaier S, Hug F, Hansch GM (2004) Granzyme B and perforin: constitutive expression in human polymorphonuclear neutrophils. Blood 103:1099–1104
Watanabe M, Wallace PK, Keler T, Deo YM, Akewanlop C, Hayes DF (1999) Antibody-dependent cellular phagocytosis (ADCP) and antibody-dependent cellular cytotoxicity (ADCC) of breast cancer cells mediated by bispecific antibody, MDX-210. Breast Cancer Res Treat 53:199–207
Weiner LM, Murray JC, Shuptrine CW (2012) Antibody-based immunotherapy of cancer. Cell 148:1081–1084
Weng WK, Levy R (2003) Two immunoglobulin G fragment C receptor polymorphisms independently predict response to rituximab in patients with follicular lymphoma. J Clin Oncol 21:3940–3947
Wilson NS, Yang B, Yang A, Loeser S, Marsters S, Lawrence D, Li Y, Pitti R, Totpal K, Yee S, Ross S, Vernes JM, Lu Y, Adams C, Offringa R, Kelley B, Hymowitz S, Daniel D, Meng G, Ashkenazi A (2011) An Fcgamma receptor-dependent mechanism drives antibody-mediated target-receptor signalling in cancer cells. Cancer Cell 19:101–113
Wind J, Tuynman JB, Tibbe AG, Swennenhuis JF, Richel DJ, van Berge Henegouwen MI, Bemelman WA (2009) Circulating tumor cells during laparoscopic and open surgery for primary colonic cancer in portal and peripheral blood. Eur J Surg Oncol 35:942–950
You T, Hu W, Ge X, Shen J, Qin X (2011) Application of a novel inhibitor of human CD59 for the enhancement of complement-dependent cytolysis on cancer cells. Cell Mol Immunol 8:157–163
Zamai L, Ponti C, Mirandola P, Gobbi G, Papa S, Galeotti L, Cocco L, Vitale M (2007) NK cells and cancer. J Immunol 178:4011–4016
Zhang Z, Zhang M, Goldman CK, Ravetch JV, Waldmann TA (2003) Effective therapy for a murine model of adult T-cell leukemia with the humanised anti-CD52 monoclonal antibody, Campath-1H. Cancer Res 63:6453–6457
Zhao XW, van Beek EM, Schornagel K, van der Maaden H, van Houdt M, Otten MA, Finetti P, van Egmond M, Matozaki T, Kraal G, Birnbaum D, van Elsas A, Kuijpers TW, Bertucci F, van den Berg TK (2011) CD47-signal regulatory protein-alpha (SIRPalpha) interactions form a barrier for antibody-mediated tumor cell destruction. Proc Natl Acad Sci U S A 108:18342–18347
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2014 Springer International Publishing Switzerland
About this chapter
Cite this chapter
Bakema, J.E., van Egmond, M. (2014). Fc Receptor-Dependent Mechanisms of Monoclonal Antibody Therapy of Cancer. 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_17
Download citation
DOI: https://doi.org/10.1007/978-3-319-07911-0_17
Published:
Publisher Name: Springer, Cham
Print ISBN: 978-3-319-07910-3
Online ISBN: 978-3-319-07911-0
eBook Packages: Biomedical and Life SciencesBiomedical and Life Sciences (R0)