Anti-IgE Agents

  • Francesco Patalano
Part of the Progress in Inflammation Research book series (PIR)


There is little debate over the essential role of IgE in allergic reactions. During an allergic response, CD4+ T lymphocytes of the Th2 phenotype stimulate allergen-specific B cells to produce IgE molecules via the release of IL-4/IL-13. The receptors for IgE are found on a multitude of different cells and two different types have been identified: the high-affinity receptor (FcεRI) on mast cells, basophils, and antigen-presenting cells, and the low-affinity receptor (FcεRII or CD23) on B lymphocytes, monocytes/macrophages, eosinophils, dendritic cells, and epithelial cells. After interaction with allergens, IgE-armed cells release a number of inflammatory mediators and enhance and redirect antigen presentation. This cascade of events seems to have a crucial role in the generation and persistence of symptoms in allergic diseases. The development of drugs that interfere with IgE production and function may therefore represent a more specific approach to treat these pathological conditions [1, 2].


Allergic Rhinitis Allergy Clin Immunol Respir Crit Seasonal Allergic Rhinitis Late Asthmatic Response 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Heusser C, Jardieu P (1998) Therapeutic potential of anti-IgE antibodies. Curr Opin Immunol 9: 805–814CrossRefGoogle Scholar
  2. 2.
    Jardieu P (1995) Anti-IgE therapy. Curr Opin Immunol 7: 779–782PubMedCrossRefGoogle Scholar
  3. 3.
    Shimoda K, van Deuren J, Sangster MY, Sarawar SR, Carson RT, Tripp RA, Chu C, Quelle FW, Nosaka T, Vignali DA et al (1996) Lack of IL-4 induced Th2 responses and IgE class switching in mice with disrupted Stat 6 gene. Nature 380: 630–633PubMedCrossRefGoogle Scholar
  4. 4.
    Paul WE (1997) fnterleukin 4: signalling mechanisms and control of T cell differentiation. Ciba Foundation Symposium 204: 208–216PubMedGoogle Scholar
  5. 5.
    Flores-Romo L, Shields J, Hubert Y, Graber P, Aubry J-P, Gauchat J-F, Ayala G, Allet B, Gnavaz M, Bazin H et al (1993) Inhibition of an in vivo antigen-specific IgE response by antibodies to CD23. Science 261: 1036–1041CrossRefGoogle Scholar
  6. 6.
    Manning DD, Nanning JK, Reed NR (1976) Suppression of reaginic antibody (IgE) formation in mice by treatment with anti-μ antiserum. J Exp Med 144: 288–292PubMedCrossRefGoogle Scholar
  7. 7.
    Bozelka BE, McCants ML, Salvaggio JE, Lehrer SB (1992) IgE isotype suppression in anti-μ treated mice. Immunology 46: 527–532Google Scholar
  8. 8.
    Bozelka BE, McCants ML, Salvaggio JE, Lehrer SB (1885) Effect of anti-IgE on total and specific IgE levels in adult mice. Int Arch Allergy Appl Immunol 78: 51–56CrossRefGoogle Scholar
  9. 9.
    Hook WA, Berenstein E, Basciano LA, Fox PC, Siraganian RP (1981) Monoclonal antibodies to human IgE. Fed Proc 40: 986 A 41777Google Scholar
  10. 10.
    Banyash M, Eshar Z (1984) Inhibition of IgE binding to mast cells and basophils by monoclonal antibodies to murine IgE. Eur J Immunol 14: 799–807CrossRefGoogle Scholar
  11. 11.
    Chang TW, Davis FM, Sun NC, Sun CRY, MacGlashan DW, Hamilton RG (1990) Monoclonal antibodies specific for human IgE-producing B cells: a potential therapeutic for IgE-mediated allergic diseases. Bio/Technology 8: 122–126PubMedCrossRefGoogle Scholar
  12. 12.
    Heusser CH, Bews J, Brinkmann V, Delespesse G, Kilchnerr E, Ledermann F, LeGros G, Wagner K (1991) New concept of IgE regulation. Int Archs Allergy Appl Immunol 94: 87–90CrossRefGoogle Scholar
  13. 13.
    Banyash M, Kerhy M, Eshar Z (1988) Anti-IgE monoclonal antibodies directed at the Fcε receptor binding site. Mol Immunol 25: 705–711CrossRefGoogle Scholar
  14. 14.
    Davis FM, Gossett LA, Pinkston KL, Liou RS, Sun LK, Kim YW, Chang NT, Chang TW, Wagner K, Bews J et al (1993) Can anti-IgE be used to treat allergy? Springer Seminars in Immunopathology 15: 51–73PubMedCrossRefGoogle Scholar
  15. 15.
    Presta L, Shields R, O’Connels L, Lahr S, Porter J, Gorman C, Jardieu P (1994) The binding site of on human Immunoglobulin E for its high affinity receptors. J Biol Chem 269(42): 26368–26373PubMedGoogle Scholar
  16. 16.
    Nissim A, Eshar Z (1991) Localization of the Fcε receptor binding site to the third constant domain of IgE. Int Arch Allergy Appl Immunol 94: 93–95PubMedCrossRefGoogle Scholar
  17. 17.
    Weetal M, Shopes B, Holowka D, Baird B (1990) Mapping the site of interaction between murine IgE and its high affinity receptor with chimeric Ig. J Immunol 145(11): 3849–3854Google Scholar
  18. 18.
    Khazaeli MB, Saleh MN, Wheeler RH, Huster WJ, Holden H, Carrano R, LoBuglio AF (1988) Phase I trial of multiple large doses of murine monoclonal antibody CO17-1A. II. Pharmacokinetics and immune response. J Natl Cancer Inst 80: 937–947PubMedCrossRefGoogle Scholar
  19. 19.
    Jaffers GJ, Fuller TC, Cosimi AB, Russel PS, Winn HJ, Colvin RB (1986) Monoclonal antibody therapy: anti-idiotypic and non-anti-idiotypic antibodies to OKT3 arising despite intense immunosuppression. Transplantation 41: 572–578PubMedCrossRefGoogle Scholar
  20. 20.
    Shawler DL, Bartholomew RM, Smith LM, Dillman RO (1985) Human immune response to multiple injection of murine monoclonal IgG. J Immunol 135: 1530–1535PubMedGoogle Scholar
  21. 21.
    Sears HF, Herlyn D, Steplewski Z, Koprowski H (1984) Effects of monoclonal antibody immunotherapy on patients with gastrointestinal adenocarcinoma. J Biol Response Mod 3: 138–150PubMedGoogle Scholar
  22. 22.
    Miller RA, Oseroff AR, Stratte PT, Levy R (1983) Monoclonal antibody therapeutic trials in seven patients with T-cell lymphoma. Blood 62: 988–995PubMedGoogle Scholar
  23. 23.
    Kolbinger F, Saldanha J, Hardman N, Mendig MM (1993) Humanization of a mouse anti-human IgE antibody: a potential therapeutic for IgE-mediated allergies. Protein Engineering 6(8): 971–980PubMedCrossRefGoogle Scholar
  24. 24.
    Presta L, Lahr S, Shields R, Porter J, Gorman C, Fendly B, Jardieu P (1993) Humanization of an antibody directed against Immunoglobulin E. J Immunol 151(5): 2623–2632PubMedGoogle Scholar
  25. 25.
    Morrison SL, Johnson MJ, Herzenberg LA, Oi VT (1984) Chimeric human antibody molecules: mouse antigen-binding domains with human constant region domains. Proc Natl Acad Sci USA 81: 6851–6855PubMedCrossRefGoogle Scholar
  26. 26.
    Reichmann L, Clark M, Waldmann H, Winter G (1988) Reshaping human antibodies for therapy. Nature 332: 323–327CrossRefGoogle Scholar
  27. 27.
    Jones PT, Dear PH, Foote J, Neuberger MS, Winter G (1986) Replacing the complementarity-determining regions in human antibody with those from a mouse. Nature 321: 522–525PubMedCrossRefGoogle Scholar
  28. 28.
    Amit AG, Mariuzza RA, Phillips SEV, Poljak RJ (1986) Three-dimensional structure of an antigen-antibody complex at 2.8 A resolution. Science 233:747–753PubMedCrossRefGoogle Scholar
  29. 29.
    Carter P, Presta L, Gorman CM, Ridgway JBB, Henner D, Wong WLT, Rowland AM, Kotts C, Carver ME, Shepard MH (1992) Humanization of an anti-p185 HER2 antibody for human cancer therapy. Proc Natl Acad Sci USA 89: 4285–4289PubMedCrossRefGoogle Scholar
  30. 30.
    Corne J, Djukanovic R, Thomas L, Warner J, Botta L, Grandordy B, Gygax D, Huesser C, Patalano F, Richardson W et al (1997) The effect of intravenous administration of a chimeric anti-IgE antibody on serum IgE levels in atopic subjects: Efficacy, safety and pharmacokinetics. J Clin Invest 99(5): 879–887PubMedCrossRefGoogle Scholar
  31. 31.
    Togias A, Corren J, Shapiro G, Reimann JD, von Schlegell A, Wighton TG, Adelmann DC (1998) Anti-IgE treatment reduces Skin Test (ST) reactivity. J Allergy Clin Immunol 101 (1 pr2): s171 Abstract 706Google Scholar
  32. 32.
    Racine-Poon A, Botta L, Chang TW, Davis FM, Gygax D, Liou RS, Rohane P, Stahelin T, Van Steijn A, Frank W (1997) Efficacy, pharmacodynamics and pharamacokinetics of CGP 51901, an anti-immunoglobulin E chimeric monoclonal antibody, in patients with seasonal allergic rhinitis. Clin Pharmacol Ther 62: 675–690PubMedCrossRefGoogle Scholar
  33. 33.
    Casale TB, Bernstein IL, Busse WW, LaForce CF, Tinkelman DG, Stoltz RR, Dockhorn RJ, Reimann JR, Su JQ, Fick RB, Adelman DC (1997) Use of an anti-IgE humanized monoclonal antibody in ragweed-induced allergic rhinitis. J Allergy Clin Immunol 100: 110–121PubMedCrossRefGoogle Scholar
  34. 34.
    Cockcroft DW, Murdock KY (1987) Comparative effects of inhaled salbutamol, sodium cromoglycate and bechlomethasone dipropionate on allergen-induced early asthmatic responses, late asthmatic responses, and bronchial responsiveness to histamine. J Allergy Clin Immunol 79: 734–740PubMedCrossRefGoogle Scholar
  35. 35.
    Cockcroft DW, Swystun VA, Baghat R (1995) Interaction of inhaled β2 agonist and inhaled corticosteroid on airway responsiveness to allergen and methacholine. Am J Respir Crit Care Med 152: 1485–1489PubMedGoogle Scholar
  36. 36.
    Holgate ST, Robinson C, Church MK (1993) Mediators of immediate hypersensitivity. In: E Middleton Jr, CE Reed, EF Regis, NF Adkinson Jr, JW Yuninger, Busse WW (eds): Allergy principle and practice. 4th ed, Mosby, St Louis, 267–301Google Scholar
  37. 37.
    Zweiman B (1993) The late phase response: role of IgE, its receptor, and cytokines. Cur Opin Immunol 5: 950–955CrossRefGoogle Scholar
  38. 38.
    Boulet L-P, Chapman KR, Coté J, Kaira S, Bhagat R, Swystun VA, Laviolette M, Cleland LD, Deschesnes F, Su JQ et al (1997) Inhibitory effects of an anti-IgE antibody E25 on allergen-induced early asthmatic response. Am J Respir Crit Care Med 155: 1835–1840PubMedGoogle Scholar
  39. 39.
    Cockcroft DW, Swystun VA, Bhagat R (1995) Interaction of β2 agonist and inhaled corticosteroid on airway responsiveness to allergen and methacholine. Am J Respir Crit Care Med 152: 1485–1489PubMedGoogle Scholar
  40. 40.
    Fahy JV, Flemming HE, Wong HH, Liu JT, Su JQ, Reimann J, Fick RB, Jr, Boushey HA (1997) The effect of an anti-IgE monoclonal antibody on the early-and late-phase responses to allergen inhalation in asthmatic subjects. Am J Respir Crit Care Med 155: 1828–1834PubMedGoogle Scholar
  41. 41.
    Burrows B, Martinez FD, Holonen M, Barbee RA, Cline MG (1989) Association of asthma with serum IgE levels and skin test reactivity to allergens. N Engl J Med 320: 271–277PubMedCrossRefGoogle Scholar
  42. 42.
    Sears MR, Burrows B, Flannery EM, Herbison GB, Hewitt CJ, Holdaway MD. (1991) Relation between airway responsiveness and serum IgE in children with asthma and in apparently normal children. N Engl J Med 325: 1067–1071PubMedCrossRefGoogle Scholar
  43. 43.
    Sunyer J, Munoz A and the Spanish Group of the European Asthma Study (1996) Concentration of methacholine for bronchial responsiveness according to symptoms, smoking and immunoglobulin E in a population based study in Spain. Am J Respir Crit Care Med 153: 1273–1279PubMedGoogle Scholar
  44. 44.
    Pollart S, Chapman M, Fiocco G, Rose G, Platt-Mills A (1989) Epidemiology of acute asthma: IgE antibodies to common inhalant allergens as a risk factor for emergency room visits. J Allergy Clin Immunol 83: 875–882PubMedCrossRefGoogle Scholar
  45. 45.
    Fick RB, Simon SJ, Su JQ, Zeiger R and the E25 Study Group (1998) Anti-IgE (rhuM-Ab) treatment of the symptoms of moderate to severe allergic asthma. Ann Asthma Allergy Immunol 80(1): 80 Abstract 8Google Scholar
  46. 46.
    Metzger WJ, Fick RB and the E25 Asthma Study Group (1998) Corticosteroid (CS) withdrawal in a study of recombinant humanized monoclonal antibody to IgE (RhuM-Ab E25). J Allergy Clin Immunol 101 (1 pt 2): s231 Abstract 960CrossRefGoogle Scholar
  47. 47.
    MacGlashan DW, Jr, Bochner B, Adelman D, Jardieu P, Togias A, McKenzie-White J, Sterbinsky SA, Hamilton R, Lichtenstein LM (1997) Down-regulation of FcεRI expression on human basophils during anti-IgE antibody therapy. J Immunol 158: 1438–1445PubMedGoogle Scholar
  48. 48.
    Saini S, MacGlashan DW, Jr, Adelman D, Togias A, Lichtenstein LM, Blochner BS (1998) Discontinuation of anti-IgE infusions restores basophils (BASO) IgE and FcεRIα expression, and IgE-dependent histamine release. J Allergy Clin Immunol 101 (1 pt 2): s105 Abstract 437Google Scholar
  49. 49.
    Capron A, Dessaint JP, Haque A, Capron M (1982) Antibody-dependent cell-mediated cytotoxic against parasites. Progr Allergy 31: 234–267Google Scholar
  50. 50.
    Rihet P, Demuere C, Bourgois A, Prata A, Dessein A (1991). Evidence for an association between human resistance to Schistosoma mansoni and high-larval IgE levels. Eur J Immunol 21: 2679–2686PubMedCrossRefGoogle Scholar
  51. 51.
    Hagan P, Blumenthal UJ, Dunn D, Simpson AJG, Wilkins HA (1991) Human IgE, IgG4 and resistance to reinfection with Schistosoma haematohium. Nature 349: 243–245PubMedCrossRefGoogle Scholar
  52. 52.
    Welge-Roussel F, Ariault C, Damonneville M, Capron A. (1991) Functional analysis of a T cell line specific for antiidiotypic antibodies to a Schistosoma mansoni protective epitope. II. Induction of protective immunity in experimental rat schistosomiasis. J Immunol 147: 3967–3972Google Scholar
  53. 53.
    Watanabe N, Katakura K, Kobayashi A, Okumura K, Ovary Z (1989) Protective immunity and eosinophilia in IgE-deficient SJA/9 mice infected with Nippostrogylus brasiliensis and Trichinella spiralis. Proc Natl Acad Sci USA 85: 4460–4462CrossRefGoogle Scholar
  54. 54.
    Amiri P, Haak-Frendscho M, Robbins K, McKerrow J, Stewart T, Jardieu P. (1994) Anti-immunoglobulin E treatment decreases worm burden and egg production in Schistosoma mansoni infected normal and IFNγ knockout mice. J Exp Med 180: 43–51PubMedCrossRefGoogle Scholar
  55. 55.
    Fisherman E (1960) Does the allergic diathesis influence malignancy? Allergy 31: 74–78CrossRefGoogle Scholar
  56. 56.
    Allegra J, Lipton A, Harvey H, Luderer J, Brenner D, Mortel R, Semers L, Gillin M, White D, Trautlein J (1976) Decreased prevalence of immediate hypersensitivity (atopy) in a cancer population. Cancer Res 36: 3225–3226PubMedGoogle Scholar
  57. 57.
    McKee W, Arnold CA, Perlman M (1967) A double blind study of the comparative incidence of malignancy and allergy. J Allergy Clin Immunol 39: 294–301Google Scholar
  58. 58.
    Shapiro S, Heinonen O, Siskind V (1971) Cancer and allergy. Cancer 29: 386Google Scholar

Copyright information

© Springer Basel AG 1999

Authors and Affiliations

  • Francesco Patalano
    • 1
  1. 1.Project ManagementNovartis Pharma A.G.BaselSwitzerland

Personalised recommendations