Cancer and IgE pp 215-229 | Cite as

IgE as Adjuvant in Tumor Vaccination

  • Elisa A. Nigro
  • Antonio G. Siccardi
  • Luca VangelistaEmail author


Activation of the antigen-IgE-FcɛRI axis results in a potent inflammatory state. The redirection of this IgE-mediated activation of the immune system from allergic reactions toward tumors is the main theme of the new AllergoOncology field. Our particular approach has been to employ IgE as an adjuvant in anti-tumor vaccination. IgE-coated tumor cells can protect against tumor challenge, an observation that supports the involvement of IgE in anti-tumor immunity. The adjuvant effect of IgE was shown to result from eosinophil-dependent priming of the T-cell-mediated adaptive immune response. Moreover, the role of FcɛRI in IgE anti-tumor adjuvanticity has been recently demonstrated. The interaction of tumor cell-bound IgE with receptors triggers the release of mediators with following recruitment of effector cells, cell killing and tumor antigen cross-priming. Starting from these evidences, several improvements toward a simple and universal use of IgE in anti-tumor cellular vaccines have been accomplished. In view of narrowing the gap between experimental models and therapeutic applications, the field is now shifting toward a humanized systems, employing human IgE and human FcɛRIα transgenic mice.


Vaccinia Virus Vaccination Protocol Modify Vaccinia Virus Ankara Irradiate Tumor Cell Single Immunization 
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.



We wish to thank Anna Brini, David Dombrowicz and Elisa Soprana for excellent help and assistance with various aspects of the experimental systems presented here. This work was supported by the Italian MURST Cofin 2004, 2005 and 2007.


  1. 1.
    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 21:579–628CrossRefPubMedGoogle Scholar
  2. 2.
    Jensen-Jarolim E, Achatz G, Turner MC, Karagiannis S, Legrand F, Capron M, Penichet ML, Rodríguez JA, Siccardi AG, Vangelista L, Riemer AB, Gould H (2008) AllergoOncology: the role of IgE-mediated allergy in cancer. Allergy 63:1255–1266CrossRefPubMedGoogle Scholar
  3. 3.
    Moro M, Pelagi M, Fulci G, Paganelli G, Dellabona P, Casorati G, Siccardi AG, Corti A (1997) Tumor cell targeting with antibody-avidin complexes and biotinylated tumor necrosis factor alpha. Cancer Res 57:1922–1928PubMedGoogle Scholar
  4. 4.
    Gasparri A, Moro M, Curnis F, Sacchi A, Pagano S, Veglia F, Casorati G, Siccardi AG, Dellabona P, Corti A (1999) Tumor pretargeting with avidin improves the therapeutic index of biotinylated tumor necrosis factor alpha in mouse models. Cancer Res 59:2917–2923PubMedGoogle Scholar
  5. 5.
    Guidi F, Spagnoli GC, Neri G, Paganelli G, Siccardi AG, Guttinger M (1998) Three-step tumor targeting via biotin-avidin interaction as a versatile system to elicit T-cell-mediated, non-MHC-restricted cytotoxic activity against neoplastic cells. Int J Cancer 76:443–447CrossRefPubMedGoogle Scholar
  6. 6.
    Guttinger M, Guidi F, Chinol M, Reali E, Veglia F, Viale G, Paganelli G, Corti A, Siccardi AG (2000) Adoptive immunotherapy by avidin-driven cytotoxic T lymphocyte-tumor bridging. Cancer Res 60:4211–4215PubMedGoogle Scholar
  7. 7.
    Paganelli G, Grana C, Chinol M, Cremonesi M, De Cicco C, De Braud F, Robertson C, Zurrida S, Casadio C, Zoboli S, Siccardi AG, Veronesi U (1999) Antibody-guided three-step therapy for high grade glioma with yttrium-90 biotin. Eur J Nucl Med 26:348–357CrossRefPubMedGoogle Scholar
  8. 8.
    Siccardi AG, Paganelli G, Pontiroli AE, Pelagi M, Magnani P, Viale G, Faglia G, Fazio F (1996) In vivo imaging of chromogranin A-positive endocrine tumours by three-step monoclonal antibody targeting. Eur J Nucl Med 23:1455–1459CrossRefPubMedGoogle Scholar
  9. 9.
    Robbins PF, Kantor JA, Salgaller M, Hand PH, Fernsten PD, Schlom J (1991) Transduction and expression of the human carcinoembryonic antigen gene in a murine colon carcinoma cell line. Cancer Res 51:3657–3662PubMedGoogle Scholar
  10. 10.
    Reali E, Greiner JW, Corti A, Gould HJ, Bottazzoli F, Paganelli G, Schlom J, Siccardi AG (2001) IgEs targeted on tumor cells: therapeutic activity and potential in the design of tumor vaccines. Cancer Res 61:5517–5522PubMedGoogle Scholar
  11. 11.
    Vangelista L, Soprana E, Cesco-Gaspere M, Mandiola P, Di Lullo G, Fucci RN, Codazzi F, Palini A, Paganelli G, Burrone OR, Siccardi AG (2005) Membrane IgE binds and activates Fc epsilon RI in an antigen-independent manner. J Immunol 174:5602–5611PubMedGoogle Scholar
  12. 12.
    Wittek R, Moss B (1980) Tandem repeats within the inverted terminal repetition of vaccinia virus DNA. Cell 21:277–284CrossRefPubMedGoogle Scholar
  13. 13.
    Moss B (1996) Genetically engineered poxviruses for recombinant gene expression, vaccination, and safety. Proc Natl Acad Sci USA 93:11341–11348CrossRefPubMedGoogle Scholar
  14. 14.
    Brochier B, Costy F, Pastoret PP (1995) Elimination of fox rabies from Belgium using a recombinant vaccinia-rabies vaccine: an update. Vet Microbiol 46:269–279CrossRefPubMedGoogle Scholar
  15. 15.
    Nigro EA, Brini AT, Soprana E, Ambrosi A, Dombrowicz D, Siccardi AG, Vangelista L (2009) Antitumor IgE Adjuvanticity: Key Role of FcɛRI. J Immunol 183:4530–4536Google Scholar
  16. 16.
    Mayr A, Hochstein-Mintzel V, Stickl H (1975) Abstammung, eigenschaften und Verwendung des attenuierten Vaccinia-Stammes MVA. Infection 3:6–16CrossRefGoogle Scholar
  17. 17.
    Meyer H, Sutter G, Mayr A (1991) Mapping of deletions in the genome of the highly attenuated vaccinia virus MVA and their influence on virulence. J Gen Virol 72(Pt5):1031–1038CrossRefPubMedGoogle Scholar
  18. 18.
    Sutter G, Moss B (1992) Nonreplicating vaccinia vector efficiently expresses recombinant genes. Proc Natl Acad Sci USA 89:10847–10851CrossRefPubMedGoogle Scholar
  19. 19.
    Mayr A, Danner K (1978) Vaccination against pox diseases under immunosuppressive conditions. Dev Biol Stand 41:225–234PubMedGoogle Scholar
  20. 20.
    Acres B, Bonnefoy JY (2008) Clinical development of MVA-based therapeutic cancer vaccines. Expert Rev Vaccines 7:889–893CrossRefPubMedGoogle Scholar
  21. 21.
    Liu M, Acres B, Balloul JM, Bizouarne N, Paul S, Slos P, Squiban P (2004) Gene-based vaccines and immunotherapeutics. Proc Natl Acad Sci USA 101(Suppl 2):14567–14571CrossRefPubMedGoogle Scholar
  22. 22.
    McConkey SJ, Reece WH, Moorthy VS, Webster D, Dunachie S, Butcher G, Vuola JM, Blanchard TJ, Gothard P, Watkins K, Hannan CM, Everaere S, Brown K, Kester KE, Cummings J, Williams J, Heppner DG, Pathan A, Flanagan K, Arulanantham N, Roberts MT, Roy M, Smith GL, Schneider J, Peto T, Sinden RE, Gilbert SC, Hill AV (2003) Enhanced T-cell immunogenicity of plasmid DNA vaccines boosted by recombinant modified vaccinia virus Ankara in humans. Nat Med 9:729–735CrossRefPubMedGoogle Scholar
  23. 23.
    Gilbert SC, Moorthy VS, Andrews L, Pathan AA, McConkey SJ, Vuola JM, Keating SM, Berthoud T, Webster D, McShane H, Hill AV (2006) Synergistic DNA-MVA prime-boost vaccination regimes for malaria and tuberculosis. Vaccine 24:4554–4561CrossRefPubMedGoogle Scholar
  24. 24.
    Mwau M, Cebere I, Sutton J, Chikoti P, Winstone N, Wee EG, Beattie T, Chen YH, Dorrell L, McShane H, Schmidt C, Brooks M, Patel S, Roberts J, Conlon C, Rowland-Jones SL, Bwayo JJ, McMichael AJ, Hanke T (2004) A human immunodeficiency virus 1 (HIV-1) clade A vaccine in clinical trials: stimulation of HIV-specific T-cell responses by DNA and recombinant modified vaccinia virus Ankara (MVA) vaccines in humans. J Gen Virol 85:911–919CrossRefPubMedGoogle Scholar
  25. 25.
    Staib C, Drexler I, Ohlmann M, Wintersperger S, Erfle V, Sutter G (2000) Transient host range selection for genetic engineering of modified vaccinia virus Ankara. BioTechniques 28:1137–1142, 1144–1146, 1148PubMedGoogle Scholar
  26. 26.
    Staib C, Lowel M, Erfle V, Sutter G (2003) Improved host range selection for recombinant modified vaccinia virus Ankara. BioTechniques 34:694–696, 698, 700PubMedGoogle Scholar
  27. 27.
    Di Lullo G, Soprana E, Panigada M, Palini A, Erfle V, Staib C, Sutter G, Siccardi AG (2009) Marker gene swapping facilitates recombinant Modified Vaccinia Virus Ankara production by host-range selection. J Virol Methods 156:37–43CrossRefPubMedGoogle Scholar
  28. 28.
    Dombrowicz D, Flamand V, Brigman KK, Koller BH, Kinet JP (1993) Abolition of anaphylaxis by targeted disruption of the high affinity immunoglobulin E receptor alpha chain gene. Cell 75:969–976CrossRefPubMedGoogle Scholar
  29. 29.
    Yu P, Kosco-Vilbois M, Richards M, Kohler G, Lamers MC (1994) Negative feedback regulation of IgE synthesis by murine CD23. Nature 369:753–756CrossRefPubMedGoogle Scholar
  30. 30.
    Benigni F, Zimmermann VS, Hugues S, Caserta S, Basso V, Rivino L, Ingulli E, Malherbe L, Glaichenhaus N, Mondino A (2005) Phenotype and homing of CD4 tumor-specific T-cells is modulated by tumor bulk. J Immunol 175:739–748PubMedGoogle Scholar
  31. 31.
    Rosato A, Zoso A, Milan G, Macino B, Dalla Santa S, Tosello V, Di Carlo E, Musiani P, Whalen RG, Zanovello P (2003) Individual analysis of mice vaccinated against a weakly immunogenic self tumor-specific antigen reveals a correlation between CD8 T-cell response and antitumor efficacy. J Immunol 171:5172–5179PubMedGoogle Scholar
  32. 32.
    Vangelista L (2003) Current progress in the understanding of IgE-Fc epsilon RI interaction. Int Arch Allergy Immunol 131:222–233CrossRefPubMedGoogle Scholar
  33. 33.
    Venkitaraman AR, Williams GT, Dariavach P, Neuberger MS (1991) The B-cell antigen receptor of the five immunoglobulin classes. Nature 352:777–781CrossRefPubMedGoogle Scholar
  34. 34.
    Dombrowicz D, Brini AT, Flamand V, Hicks E, Snouwaert JN, Kinet JP, Koller BH (1996) Anaphylaxis mediated through a humanized high affinity IgE receptor. J Immunol 157:1645–1651PubMedGoogle Scholar
  35. 35.
    Dombrowicz D, Lin S, Flamand V, Brini AT, Koller BH, Kinet JP (1998) Allergy-associated FcR beta is a molecular amplifier of IgE- and IgG-b in vivo responses. Immunity 8:517–529CrossRefPubMedGoogle Scholar
  36. 36.
    Kayaba H, Dombrowicz D, Woerly G, Papin JP, Loiseau S, Capron M (2001) Human eosinophils and human high affinity IgE receptor transgenic mouse eosinophils express low levels of high affinity IgE receptor, but release IL-10 upon receptor activation. J Immunol 167:995–1003PubMedGoogle Scholar
  37. 37.
    Kinet JP (1999) The high-affinity IgE receptor (Fc epsilon RI): from physiology to pathology. Annu Rev Immunol 17:931–972CrossRefPubMedGoogle Scholar
  38. 38.
    Hodge JW, Higgins J, Schlom J (2009) Harnessing the unique local immunostimulatory properties of modified vaccinia Ankara (MVA) virus to generate superior tumor-specific immune responses and antitumor activity in a diversified prime and boost vaccine regimen. Vaccine 27:4475–4482Google Scholar
  39. 39.
    Garman SC, Wurzburg BA, Tarchevskaya SS, Kinet JP, Jardetzky TS (2000) Structure of the Fc fragment of human IgE bound to its high-affinity receptor Fc epsilonRI alpha. Nature 406:259–266CrossRefPubMedGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2010

Authors and Affiliations

  • Elisa A. Nigro
    • 1
  • Antonio G. Siccardi
    • 1
  • Luca Vangelista
    • 1
    Email author
  1. 1.Department of Biology and GeneticsUniversity of Milan and San Raffaele Scientific InstituteMilanItaly

Personalised recommendations