Cancer Immunology, Immunotherapy

, Volume 61, Issue 9, pp 1547–1564 | Cite as

Recombinant IgE antibodies for passive immunotherapy of solid tumours: from concept towards clinical application

  • Sophia N. Karagiannis
  • Debra H. Josephs
  • Panagiotis Karagiannis
  • Amy E. Gilbert
  • Louise Saul
  • Sarah M. Rudman
  • Tihomir Dodev
  • Alexander Koers
  • Philip J. Blower
  • Christopher Corrigan
  • Andrew J. Beavil
  • James F. Spicer
  • Frank O. Nestle
  • Hannah J. Gould
Symposium-in-writing paper


Therapeutic antibodies have revolutionised treatment of some cancers and improved prognosis for many patients. Over half of those available are approved for haematological malignancies, but efficacious antibodies for solid tumours are still urgently needed. Clinically available antibodies belong to the IgG class, the most prevalent antibody class in human blood, while other classes have not been extensively considered. We hypothesised that the unique properties of IgE, a class of tissue-resident antibodies commonly associated with allergies, which can trigger powerful immune responses through strong affinity for their particular receptors on effector cells, could be employed for passive immunotherapy of solid tumours such as ovarian and breast carcinomas. Our laboratory has examined this concept by evaluating two chimaeric antibodies of the same specificity (MOv18) but different isotype, an IgG1 and an IgE against the tumour antigen folate receptor α (FRα). The latter demonstrates the potency of IgE to mount superior immune responses against tumours in disease-relevant models. We identified Fcε receptor-expressing cells, monocytes/macrophages and eosinophils, activated by MOv18 IgE to kill tumour cells by mechanisms such as ADCC and ADCP. We also applied this notion to a marketed therapeutic, the humanised IgG1 antibody trastuzumab and engineered an IgE counterpart, which retained the functions of trastuzumab in restricting proliferation of HER2/neu-expressing tumour cells but also activated effector cells to kill tumour cells by different mechanisms. On-going efficacy, safety evaluations and future first-in-man clinical studies of IgE therapeutics constitute key metrics for this concept, providing new scope for antibody immunotherapies for solid tumours.


IgE Tumour immunotherapy FRα/FBP Monocytes/macrophages MOv18 IgE Allergooncology symposium-in-writing HER2/neu IgG Trastuzumab Basophils Eosinophils Mast cells Solid tumours ADCC ADCP Ovarian carcinomas Breast carcinomas 



Folate-binding protein/folate receptor alpha


Antibody-dependent cell-mediated cytotoxicity


Antibody-dependent cell-mediated phagocytosis


Fc epsilon Receptor I


Human epidermal growth factor receptor 2


FcεRI alpha



The authors acknowledge support from Cancer Research UK (C30122/A11527); This work was supported by the Department of Health via the National Institute for Health Research (NIHR) comprehensive Biomedical Research Centre award to Guy’s and St Thomas’ NHS Foundation Trust in partnership with King’s College London and King’s College Hospital NHS Foundation Trust; CR UK/EPSRC/MRC/NIHR KCL/UCL Comprehensive Cancer Imaging Centre (C1519/A10331); KCL Experimental Cancer Medicine Centre, jointly funded by Cancer Research UK, the National Institute for Health Research, Welsh Assembly Government, HSC R&D Office for Northern Ireland and Chief Scientist Office, Scotland.

Conflict of interest

The authors declare that they have no conflict of interest.


  1. 1.
    Weiner LM, Surana R, Wang S (2010) Monoclonal antibodies: versatile platforms for cancer immunotherapy. Nat Rev Immunol 10:317–327PubMedCrossRefGoogle Scholar
  2. 2.
    Li J, Zhu Z (2010) Research and development of next generation of antibody-based therapeutics. Acta Pharmacol Sin 31:1198–1207PubMedCrossRefGoogle Scholar
  3. 3.
    Dillman RO (2001) The history and rationale for monoclonal antibodies in the treatment of hematologic malignancy. Curr Pharm Biotechnol 2:293–300PubMedCrossRefGoogle Scholar
  4. 4.
    Markman B, Tabernero J (2010) Monoclonal antibodies in solid tumours. Curr Clin Pharmacol 5:160–165PubMedCrossRefGoogle Scholar
  5. 5.
    Dimitrov DS, Marks JD (2009) Therapeutic antibodies: current state and future trends–is a paradigm change coming soon? Methods Mol Biol 525:1–27, xiiiGoogle Scholar
  6. 6.
    Bruggemann M, Williams GT, Bindon CI, Clark MR, Walker MR, Jefferis R, Waldmann H, Neuberger MS (1987) Comparison of the effector functions of human immunoglobulins using a matched set of chimeric antibodies. J Exp Med 166:1351–1361PubMedCrossRefGoogle Scholar
  7. 7.
    Alduaij W, Illidge TM (2011) The future of anti-CD20 monoclonal antibodies: are we making progress? Blood 117:2993–3001PubMedCrossRefGoogle Scholar
  8. 8.
    Dechant M, Valerius T (2001) IgA antibodies for cancer therapy. Crit Rev Oncol Hematol 39:69–77PubMedCrossRefGoogle Scholar
  9. 9.
    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 186:3770–3778PubMedCrossRefGoogle Scholar
  10. 10.
    Dechant M, Vidarsson G, Stockmeyer B, Repp R, Glennie MJ, Gramatzki M, van De Winkel JG, Valerius T (2002) Chimeric IgA antibodies against HLA class II effectively trigger lymphoma cell killing. Blood 100:4574–4580PubMedCrossRefGoogle Scholar
  11. 11.
    Dyer MJ, Hale G, Hayhoe FG, Waldmann H (1989) Effects of CAMPATH-1 antibodies in vivo in patients with lymphoid malignancies: influence of antibody isotype. Blood 73:1431–1439PubMedGoogle Scholar
  12. 12.
    Imai M, Landen C, Ohta R, Cheung NK, Tomlinson S (2005) Complement-mediated mechanisms in anti-GD2 monoclonal antibody therapy of murine metastatic cancer. Cancer Res 65:10562–10568PubMedCrossRefGoogle Scholar
  13. 13.
    Weiner GJ (2007) Monoclonal antibody mechanisms of action in cancer. Immunol Res 39:271–278PubMedCrossRefGoogle Scholar
  14. 14.
    Kaehler KC, Piel S, Livingstone E, Schilling B, Hauschild A, Schadendorf D (2010) Update on immunologic therapy with anti-CTLA-4 antibodies in melanoma: identification of clinical and biological response patterns, immune-related adverse events, and their management. Semin Oncol 37:485–498PubMedCrossRefGoogle Scholar
  15. 15.
    Cai J, Han S, Qing R, Liao D, Law B, Boulton ME (2011) In pursuit of new anti-angiogenic therapies for cancer treatment. Front Biosci 16:803–814PubMedCrossRefGoogle Scholar
  16. 16.
    Ascierto PA, Simeone E, Sznol M, Fu YX, Melero I (2010) Clinical experiences with anti-CD137 and anti-PD1 therapeutic antibodies. Semin Oncol 37:508–516PubMedCrossRefGoogle Scholar
  17. 17.
    Govindan SV, Goldenberg DM (2010) New antibody conjugates in cancer therapy. ScientificWorldJournal 10:2070–2089PubMedCrossRefGoogle Scholar
  18. 18.
    Kubota T, Niwa R, Satoh M, Akinaga S, Shitara K, Hanai N (2009) Engineered therapeutic antibodies with improved effector functions. Cancer Sci 100:1566–1572PubMedCrossRefGoogle Scholar
  19. 19.
    Hellman L (2007) Regulation of IgE homeostasis, and the identification of potential targets for therapeutic intervention. Biomed Pharmacother 61:34–49PubMedCrossRefGoogle Scholar
  20. 20.
    Ravetch JV, Kinet JP (1991) Fc receptors. Annu Rev Immunol 9:457–492PubMedCrossRefGoogle Scholar
  21. 21.
    Brigati C, Noonan DM, Albini A, Benelli R (2002) Tumors and inflammatory infiltrates: friends or foes? Clin Exp Metastasis 19:247–258PubMedCrossRefGoogle Scholar
  22. 22.
    Kraft S, Kinet JP (2007) New developments in FcepsilonRI regulation, function and inhibition. Nat Rev Immunol 7:365–378PubMedCrossRefGoogle Scholar
  23. 23.
    Maenaka K, van der Merwe PA, Stuart DI, Jones EY, Sondermann P (2001) The human low affinity Fcgamma receptors IIa, IIb, and III bind IgG with fast kinetics and distinct thermodynamic properties. J Biol Chem 276:44898–44904PubMedCrossRefGoogle Scholar
  24. 24.
    Gould HJ, Sutton BJ (2008) IgE in allergy and asthma today. Nat Rev Immunol 8:205–217PubMedCrossRefGoogle Scholar
  25. 25.
    Gould HJ, Sutton BJ, Beavil AJ, Beavil RL, McCloskey N, Coker HA, Fear D, Smurthwaite L (2003) The biology of IGE and the basis of allergic disease. Annu Rev Immunol 21:579–628PubMedCrossRefGoogle Scholar
  26. 26.
    Maurer D, Fiebiger S, Ebner C, Reininger B, Fischer GF, Wichlas S, Jouvin MH, Schmitt-Egenolf M, Kraft D, Kinet JP, Stingl G (1996) Peripheral blood dendritic cells express Fc epsilon RI as a complex composed of Fc epsilon RI alpha- and Fc epsilon RI gamma-chains and can use this receptor for IgE-mediated allergen presentation. J Immunol 157:607–616PubMedGoogle Scholar
  27. 27.
    Maurer D, Fiebiger E, Reininger B, Wolff-Winiski B, Jouvin MH, Kilgus O, Kinet JP, Stingl G (1994) Expression of functional high affinity immunoglobulin E receptors (Fc epsilon RI) on monocytes of atopic individuals. J Exp Med 179:745–750PubMedCrossRefGoogle Scholar
  28. 28.
    Hibbert RG, Teriete P, Grundy GJ, Beavil RL, Reljic R, Holers VM, Hannan JP, Sutton BJ, Gould HJ, McDonnell JM (2005) The structure of human CD23 and its interactions with IgE and CD21. J Exp Med 202:751–760PubMedCrossRefGoogle Scholar
  29. 29.
    Hlavacek WS, Perelson AS, Sulzer B, Bold J, Paar J, Gorman W, Posner RG (1999) Quantifying aggregation of IgE-FcepsilonRI by multivalent antigen. Biophys J 76:2421–2431PubMedCrossRefGoogle Scholar
  30. 30.
    Matsuda H, Watanabe N, Kiso Y, Hirota S, Ushio H, Kannan Y, Azuma M, Koyama H, Kitamura Y (1990) Necessity of IgE antibodies and mast cells for manifestation of resistance against larval Haemaphysalis longicornis ticks in mice. J Immunol 144:259–262PubMedGoogle Scholar
  31. 31.
    Dombrowicz D, Quatannens B, Papin JP, Capron A, Capron M (2000) Expression of a functional Fc epsilon RI on rat eosinophils and macrophages. J Immunol 165:1266–1271PubMedGoogle Scholar
  32. 32.
    Mossalayi MD, Arock M, Mazier D, Vincendeau P, Vouldoukis I (1999) The human immune response during cutaneous leishmaniasis: NO problem. Parasitol Today 15:342–345PubMedCrossRefGoogle Scholar
  33. 33.
    Vouldoukis I, Riveros-Moreno V, Dugas B, Ouaaz F, Becherel P, Debre P, Moncada S, Mossalayi MD (1995) The killing of Leishmania major by human macrophages is mediated by nitric oxide induced after ligation of the Fc epsilon RII/CD23 surface antigen. Proc Natl Acad Sci USA 92:7804–7808PubMedCrossRefGoogle Scholar
  34. 34.
    Lecoanet-Henchoz S, Plater-Zyberk C, Graber P, Gretener D, Aubry JP, Conrad DH, Bonnefoy JY (1997) Mouse CD23 regulates monocyte activation through an interaction with the adhesion molecule CD11b/CD18. Eur J Immunol 27:2290–2294PubMedCrossRefGoogle Scholar
  35. 35.
    Yokota A, Kikutani H, Tanaka T, Sato R, Barsumian EL, Suemura M, Kishimoto T (1988) Two species of human Fc epsilon receptor II (Fc epsilon RII/CD23): tissue-specific and IL-4-specific regulation of gene expression. Cell 55:611–618PubMedCrossRefGoogle Scholar
  36. 36.
    de Waal Malefyt R, Figdor CG, Huijbens R, Mohan-Peterson S, Bennett B, Culpepper J, Dang W, Zurawski G, de Vries JE (1993) Effects of IL-13 on phenotype, cytokine production, and cytotoxic function of human monocytes. Comparison with IL-4 and modulation by IFN-gamma or IL-10. J Immunol 151:6370–6381PubMedGoogle Scholar
  37. 37.
    Vecchiarelli A, Siracusa A, Monari C, Pietrella D, Retini C, Severini C (1994) Cytokine regulation of low-affinity IgE receptor (CD23) on monocytes from asthmatic subjects. Clin Exp Immunol 97:248–253PubMedCrossRefGoogle Scholar
  38. 38.
    Spittler A, Oehler R, Goetzinger P, Holzer S, Reissner CM, Leutmezer F, Rath V, Wrba F, Fuegger R, Boltz-Nitulescu G, Roth E (1997) Low glutamine concentrations induce phenotypical and functional differentiation of U937 myelomonocytic cells. J Nutr 127:2151–2157PubMedGoogle Scholar
  39. 39.
    Spittler A, Schiller C, Willheim M, Tempfer C, Winkler S, Boltz-Nitulescu G (1995) IL-10 augments CD23 expression on U937 cells and down-regulates IL-4-driven CD23 expression on cultured human blood monocytes: effects of IL-10 and other cytokines on cell phenotype and phagocytosis. Immunology 85:311–317PubMedGoogle Scholar
  40. 40.
    Pages F, Galon J, Dieu-Nosjean MC, Tartour E, Sautes-Fridman C, Fridman WH (2010) Immune infiltration in human tumors: a prognostic factor that should not be ignored. Oncogene 29:1093–1102PubMedCrossRefGoogle Scholar
  41. 41.
    Lewis CE, Pollard JW (2006) Distinct role of macrophages in different tumor microenvironments. Cancer Res 66:605–612PubMedCrossRefGoogle Scholar
  42. 42.
    Lin EY, Pollard JW (2004) Role of infiltrated leucocytes in tumour growth and spread. Br J Cancer 90:2053–2058PubMedCrossRefGoogle Scholar
  43. 43.
    Kalli KR, Oberg AL, Keeney GL, Christianson TJ, Low PS, Knutson KL, Hartmann LC (2008) Folate receptor alpha as a tumor target in epithelial ovarian cancer. Gynecol Oncol 108:619–626PubMedCrossRefGoogle Scholar
  44. 44.
    Toffoli G, Russo A, Gallo A, Cernigoi C, Miotti S, Sorio R, Tumolo S, Boiocchi M (1998) Expression of folate binding protein as a prognostic factor for response to platinum-containing chemotherapy and survival in human ovarian cancer. Int J Cancer 79:121–126PubMedCrossRefGoogle Scholar
  45. 45.
    Parker N, Turk MJ, Westrick E, Lewis JD, Low PS, Leamon CP (2005) Folate receptor expression in carcinomas and normal tissues determined by a quantitative radioligand binding assay. Anal Biochem 338:284–293PubMedCrossRefGoogle Scholar
  46. 46.
    Toffoli G, Cernigoi C, Russo A, Gallo A, Bagnoli M, Boiocchi M (1997) Overexpression of folate binding protein in ovarian cancers. Int J Cancer 74:193–198PubMedCrossRefGoogle Scholar
  47. 47.
    Smith AE, Pinkney M, Piggott NH, Calvert H, Milton ID, Lunec J (2007) A novel monoclonal antibody for detection of folate receptor alpha in paraffin-embedded tissues. Hybridoma (Larchmt) 26:281–288CrossRefGoogle Scholar
  48. 48.
    Forster MD, Ormerod MG, Agarwal R, Kaye SB, Jackman AL (2007) Flow cytometric method for determining folate receptor expression on ovarian carcinoma cells. Cytometry A 71:945–950PubMedGoogle Scholar
  49. 49.
    Coney LR, Tomassetti A, Carayannopoulos L, Frasca V, Kamen BA, Colnaghi MI, Zurawski VR Jr (1991) Cloning of a tumor-associated antigen: MOv18 and MOv19 antibodies recognize a folate-binding protein. Cancer Res 51:6125–6132PubMedGoogle Scholar
  50. 50.
    Coney LR, Mezzanzanica D, Sanborn D, Casalini P, Colnaghi MI, Zurawski VR Jr (1994) Chimeric murine-human antibodies directed against folate binding receptor are efficient mediators of ovarian carcinoma cell killing. Cancer Res 54:2448–2455PubMedGoogle Scholar
  51. 51.
    Gould HJ, Mackay GA, Karagiannis SN, O’Toole CM, Marsh PJ, Daniel BE, Coney LR, Zurawski VR Jr, Joseph M, Capron M, Gilbert M, Murphy GF, Korngold R (1999) Comparison of IgE and IgG antibody-dependent cytotoxicity in vitro and in a SCID mouse xenograft model of ovarian carcinoma. Eur J Immunol 29:3527–3537PubMedCrossRefGoogle Scholar
  52. 52.
    Buist MR, Molthoff CF, Kenemans P, Meijer CJ (1995) Distribution of OV-TL 3 and MOv18 in normal and malignant ovarian tissue. J Clin Pathol 48:631–636PubMedCrossRefGoogle Scholar
  53. 53.
    Molthoff CF, Buist MR, Kenemans P, Pinedo HM, Boven E (1992) Experimental and clinical analysis of the characteristics of a chimeric monoclonal antibody, MOv18, reactive with an ovarian cancer-associated antigen. J Nucl Med 33:2000–2005PubMedGoogle Scholar
  54. 54.
    Molthoff CF, Prinssen HM, Kenemans P, van Hof AC, den Hollander W, Verheijen RH (1997) Escalating protein doses of chimeric monoclonal antibody MOv18 immunoglobulin G in ovarian carcinoma patients: a phase I study. Cancer 80:2712–2720PubMedCrossRefGoogle Scholar
  55. 55.
    van Zanten-Przybysz I, Molthoff CF, Roos JC, Plaizier MA, Visser GW, Pijpers R, Kenemans P, Verheijen RH (2000) Radioimmunotherapy with intravenously administered 131I-labeled chimeric monoclonal antibody MOv18 in patients with ovarian cancer. J Nucl Med 41:1168–1176PubMedGoogle Scholar
  56. 56.
    van Zanten-Przybysz I, Molthoff CF, Roos JC, Verheijen RH, van Hof A, Buist MR, Prinssen HM, den Hollander W, Kenemans P (2001) Influence of the route of administration on targeting of ovarian cancer with the chimeric monoclonal antibody MOv18: i.v. vs. i.p. Int J Cancer 92:106–114PubMedGoogle Scholar
  57. 57.
    Crippa F, Bolis G, Seregni E, Gavoni N, Scarfone G, Ferraris C, Buraggi GL, Bombardieri E (1995) Single-dose intraperitoneal radioimmunotherapy with the murine monoclonal antibody I-131 MOv18: clinical results in patients with minimal residual disease of ovarian cancer. Eur J Cancer 31A:686–690PubMedCrossRefGoogle Scholar
  58. 58.
    Crippa F, Buraggi GL, Di Re E, Gasparini M, Seregni E, Canevari S, Gadina M, Presti M, Marini A, Seccamani E (1991) Radioimmunoscintigraphy of ovarian cancer with the MOv18 monoclonal antibody. Eur J Cancer 27:724–729PubMedCrossRefGoogle Scholar
  59. 59.
    Coliva A, Zacchetti A, Luison E, Tomassetti A, Bongarzone I, Seregni E, Bombardieri E, Martin F, Giussani A, Figini M, Canevari S (2005) 90Y Labeling of monoclonal antibody MOv18 and preclinical validation for radioimmunotherapy of human ovarian carcinomas. Cancer Immunol Immunother 54:1200–1213PubMedCrossRefGoogle Scholar
  60. 60.
    Spannuth WA, Sood AK, Coleman RL (2010) Farletuzumab in epithelial ovarian carcinoma. Expert Opin Biol Ther 10:431–437PubMedCrossRefGoogle Scholar
  61. 61.
    Kane MA, Elwood PC, Portillo RM, Antony AC, Najfeld V, Finley A, Waxman S, Kolhouse JF (1988) Influence on immunoreactive folate-binding proteins of extracellular folate concentration in cultured human cells. J Clin Invest 81:1398–1406PubMedCrossRefGoogle Scholar
  62. 62.
    Luhrs CA, Pitiranggon P, da Costa M, Rothenberg SP, Slomiany BL, Brink L, Tous GI, Stein S (1987) Purified membrane and soluble folate binding proteins from cultured KB cells have similar amino acid compositions and molecular weights but differ in fatty acid acylation. Proc Natl Acad Sci USA 84:6546–6549PubMedCrossRefGoogle Scholar
  63. 63.
    Karagiannis SN, Bracher MG, Beavil RL, Beavil AJ, Hunt J, McCloskey N, Thompson RG, East N, Burke F, Sutton BJ, Dombrowicz D, Balkwill FR, Gould HJ (2008) Role of IgE receptors in IgE antibody-dependent cytotoxicity and phagocytosis of ovarian tumor cells by human monocytic cells. Cancer Immunol Immunother 57:247–263PubMedCrossRefGoogle Scholar
  64. 64.
    Karagiannis SN, Bracher MG, Hunt J, McCloskey N, Beavil RL, Beavil AJ, Fear DJ, Thompson RG, East N, Burke F, Moore RJ, Dombrowicz DD, Balkwill FR, Gould HJ (2007) IgE-antibody-dependent immunotherapy of solid tumors: cytotoxic and phagocytic mechanisms of eradication of ovarian cancer cells. J Immunol 179:2832–2843PubMedGoogle Scholar
  65. 65.
    Karagiannis SN, Wang Q, East N, Burke F, Riffard S, Bracher MG, Thompson RG, Durham SR, Schwartz LB, Balkwill FR, Gould HJ (2003) Activity of human monocytes in IgE antibody-dependent surveillance and killing of ovarian tumor cells. Eur J Immunol 33:1030–1040PubMedCrossRefGoogle Scholar
  66. 66.
    Jackson DJ, Kumpel BM (1997) Optimisation of human anti-tetanus toxoid antibody responses and location of human cells in SCID mice transplanted with human peripheral blood leucocytes. Hum Antibodies 8:181–188PubMedGoogle Scholar
  67. 67.
    Albertsson PA, Basse PH, Hokland M, Goldfarb RH, Nagelkerke JF, Nannmark U, Kuppen PJK (2003) NK cells and the tumour microenvironment: implications for NK-cell function and anti-tumour activity. Trends Immunol 24:603–609PubMedCrossRefGoogle Scholar
  68. 68.
    Karagiannis SN, Nestle FO, Gould HJ (2010) IgE interacts with potent effector cells against tumors: ADCC and ADCP. In: Penichet ML, Jensen-Jarolim E (eds) Cancer and IgE. Springer, New York, pp 185–213CrossRefGoogle Scholar
  69. 69.
    Dechant M, Beyer T, Schneider-Merck T, Weisner W, Peipp M, van de Winkel JG, Valerius T (2007) Effector mechanisms of recombinant IgA antibodies against epidermal growth factor receptor. J Immunol 179:2936–2943PubMedGoogle Scholar
  70. 70.
    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 174:5472–5480PubMedGoogle Scholar
  71. 71.
    Zhao J, Kuroki M, Shibaguchi H, Wang L, Huo Q, Takami N, Tanaka T, Kinugasa T (2008) Recombinant human monoclonal igA antibody against CEA to recruit neutrophils to CEA-expressing cells. Oncol Res 17:217–222PubMedCrossRefGoogle Scholar
  72. 72.
    Papazahariadou M, Athanasiadis GI, Papadopoulos E, Symeonidou I, Hatzistilianou M, Castellani ML, Bhattacharya K, Shanmugham LN, Conti P, Frydas S (2007) Involvement of NK cells against tumors and parasites. Int J Biol Markers 22:144–153PubMedGoogle Scholar
  73. 73.
    Bracher M, Gould HJ, Sutton BJ, Dombrowicz D, Karagiannis SN (2007) Three-colour flow cytometric method to measure antibody-dependent tumour cell killing by cytotoxicity and phagocytosis. J Immunol Methods 323:160–171PubMedCrossRefGoogle Scholar
  74. 74.
    Sihra BS, Kon OM, Grant JA, Kay AB (1997) Expression of high-affinity IgE receptors (Fc epsilon RI) on peripheral blood basophils, monocytes, and eosinophils in atopic and nonatopic subjects: relationship to total serum IgE concentrations. J Allergy Clin Immunol 99:699–706PubMedCrossRefGoogle Scholar
  75. 75.
    Ying S, Barata LT, Meng Q, Grant JA, Barkans J, Durham SR, Kay AB (1998) High-affinity immunoglobulin E receptor (Fc epsilon RI)-bearing eosinophils, mast cells, macrophages and Langerhans’ cells in allergen-induced late-phase cutaneous reactions in atopic subjects. Immunology 93:281–288PubMedCrossRefGoogle Scholar
  76. 76.
    Rudman SM, Josephs DH, Cambrook H, Karagiannis P, Gilbert AE, Dodev T, Hunt J, Koers A, Montes A, Taams L, Canevari S, Figini M, Blower PJ, Beavil AJ, Nicodemus CF, Corrigan C, Kaye SB, Nestle FO, Gould HJ, Spicer JF, Karagiannis SN (2011) Harnessing engineered antibodies of the IgE class to combat malignancy: initial assessment of FcvarepsilonRI-mediated basophil activation by a tumour-specific IgE antibody to evaluate the risk of type I hypersensitivity. Clin Exp Allergy 41:1400–1413PubMedCrossRefGoogle Scholar
  77. 77.
    Karagiannis P, Singer J, Hunt J, Gan SK, Rudman SM, Mechtcheriakova D, Knittelfelder R, Daniels TR, Hobson PS, Beavil AJ, Spicer J, Nestle FO, Penichet ML, Gould HJ, Jensen-Jarolim E, Karagiannis SN (2009) Characterisation of an engineered trastuzumab IgE antibody and effector cell mechanisms targeting HER2/neu-positive tumour cells. Cancer Immunol Immunother 58:915–930PubMedCrossRefGoogle Scholar
  78. 78.
    Nagy E, Berczi I, Sehon AH (1991) Growth inhibition of murine mammary carcinoma by monoclonal IgE antibodies specific for the mammary tumor virus. Cancer Immunol Immunother 34:63–69PubMedCrossRefGoogle Scholar
  79. 79.
    Duarte J, Deshpande P, Guiyedi V, Mecheri S, Fesel C, Cazenave PA, Mishra GC, Kombila M, Pied S (2007) Total and functional parasite specific IgE responses in Plasmodium falciparum-infected patients exhibiting different clinical status. Malar J 6:1PubMedCrossRefGoogle Scholar
  80. 80.
    Frossi B, De Carli M, Pucillo C (2004) The mast cell: an antenna of the microenvironment that directs the immune response. J Leukoc Biol 75:579–585PubMedCrossRefGoogle Scholar
  81. 81.
    Jensen-Jarolim E, Singer J (2011) Why could passive Immunoglobulin E antibody therapy be safe in clinical oncology? Clin Exp Allergy 41:1337–1340PubMedCrossRefGoogle Scholar
  82. 82.
    Lin RY, Schwartz LB, Curry A, Pesola GR, Knight RJ, Lee HS, Bakalchuk L, Tenenbaum C, Westfal RE (2000) Histamine and tryptase levels in patients with acute allergic reactions: an emergency department-based study. J Allergy Clin Immunol 106:65–71PubMedCrossRefGoogle Scholar
  83. 83.
    De Week AL, Sanz ML, Gamboa PM, Aberer W, Sturm G, Bilo MB, Montroni M, Blanca M, Torres MJ, Mayorga L, Campi P, Manfredi M, Drouet M, Sainte-Laudy J, Romano A, Merk H, Weber JM, Jermann TM (2009) Diagnosis of immediate-type beta-lactam allergy in vitro by flow-cytometric basophil activation test and sulfidoleukotriene production: a multicenter study. J Investig Allergol Clin Immunol 19:91–109PubMedGoogle Scholar
  84. 84.
    De Week AL, Sanz ML, Gamboa PM, Aberer W, Bienvenu J, Blanca M, Demoly P, Ebo DG, Mayorga L, Monneret G, Sainte Laudy J (2008) Diagnostic tests based on human basophils: more potentials and perspectives than pitfalls. II. Technical issues. J Investig Allergol Clin Immunol 18:143–155PubMedGoogle Scholar
  85. 85.
    Lennon S, Barton C, Banken L, Gianni L, Marty M, Baselga J, Leyland-Jones B (2009) Utility of serum HER2 extracellular domain assessment in clinical decision making: pooled analysis of four trials of trastuzumab in metastatic breast cancer. J Clin Oncol 27:1685–1693PubMedCrossRefGoogle Scholar
  86. 86.
    Saka B, Aktan M, Sami U, Oner D, Sanem O, Dincol G (2006) Prognostic importance of soluble CD23 in B-cell chronic lymphocytic leukemia. Clin Lab Haematol 28:30–35PubMedCrossRefGoogle Scholar
  87. 87.
    Bansal AS, Bruce J, Hogan PG, Allen RK (1997) An assessment of peripheral immunity in patients with sarcoidosis using measurements of serum vitamin D3, cytokines and soluble CD23. Clin Exp Immunol 110:92–97PubMedCrossRefGoogle Scholar
  88. 88.
    Dehlink E, Platzer B, Baker AH, Larosa J, Pardo M, Dwyer P, Yen EH, Szepfalusi Z, Nurko S, Fiebiger E (2011) A soluble form of the high affinity IgE receptor, Fc-epsilon-RI, circulates in human serum. PLoS One 6:e19098PubMedCrossRefGoogle Scholar
  89. 89.
    Simons FE, Frew AJ, Ansotegui IJ, Bochner BS, Golden DB, Finkelman FD, Leung DY, Lotvall J, Marone G, Metcalfe DD, Muller U, Rosenwasser LJ, Sampson HA, Schwartz LB, van Hage M, Walls AF (2007) Risk assessment in anaphylaxis: current and future approaches. J Allergy Clin Immunol 120:S2–24PubMedCrossRefGoogle Scholar
  90. 90.
    Jensen-Jarolim E, Achatz G, Turner MC, Karagiannis S, Legrand F, Capron M, Penichet ML, Rodriguez JA, Siccardi AG, Vangelista L, Riemer AB, Gould H (2008) AllergoOncology: the role of IgE-mediated allergy in cancer. Allergy 63:1255–1266PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag 2011

Authors and Affiliations

  • Sophia N. Karagiannis
    • 1
    • 2
  • Debra H. Josephs
    • 1
    • 2
  • Panagiotis Karagiannis
    • 1
    • 2
  • Amy E. Gilbert
    • 1
    • 2
  • Louise Saul
    • 1
    • 2
  • Sarah M. Rudman
    • 4
  • Tihomir Dodev
    • 3
    • 5
  • Alexander Koers
    • 6
  • Philip J. Blower
    • 6
  • Christopher Corrigan
    • 5
  • Andrew J. Beavil
    • 3
    • 5
  • James F. Spicer
    • 4
  • Frank O. Nestle
    • 1
    • 2
  • Hannah J. Gould
    • 3
  1. 1.NIHR Biomedical Research Centre at Guy’s and St. Thomas’s Hospitals and King’s College LondonLondonUK
  2. 2.Cutaneous Medicine and Immunotherapy Unit, St. John’s Institute of Dermatology, Division of Genetics and Molecular Medicine, King’s College London School of Medicine, Guy’s TowerGuy’s HospitalLondonUK
  3. 3.Randall Division of Cell and Molecular Biophysics, New Hunt’s HouseKing’s College LondonLondonUK
  4. 4.Section of Research Oncology, Division of Cancer Studies, King’s College London School of MedicineGuy’s HospitalLondonUK
  5. 5.Division of Asthma, Allergy and Lung Biology, MRC and Asthma UK Centre for Allergic Mechanisms of Asthma, King’s College London School of MedicineGuy’s HospitalLondonUK
  6. 6.Department of Imaging Chemistry & Biology, Division of Imaging Sciences and Biomedical Engineering, King’s College London, The Rayne InstituteSt Thomas’ HospitalLondonUK

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