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Antitumor IgE Adjuvanticity: Key Role of FcRI¹

Elisa A. Nigro^*,, Anna T. Brini, Elisa Soprana, Alessandro Ambrosi, David Dombrowicz, Antonio G. Siccardi^*, and Luca Vangelista^2,*,

^* Department of Biology and Genetics, Department of Medical Pharmacology, University of Milan, San Raffaele Scientific Institute, Milan, Italy; and Institut National de la Santé et de la Recherche Médicale, Unité 547, Université Lille 2, Institut Pasteur de Lille, Lille, France

Working with C57BL/6 mouse tumor models, we had previously demonstrated that vaccination with IgE-coated tumor cells can protect against tumor challenge, an observation that supports the involvement of IgE in antitumor immunity. The adjuvant effect of IgE was shown to result from eosinophil-dependent priming of the T cell-mediated adaptive immune response. The protective effect is likely to be mediated by the interaction of tumor cell-bound IgE with receptors, which then trigger the release of mediators, recruitment of effector cells, cell killing and tumor Ag cross-priming. It was therefore of utmost importance to demonstrate the strict dependence of the protective effect on IgE receptor activation. First, the protective effect of IgE was confirmed in a BALB/c tumor model, in which IgE-loaded modified VV Ankara-infected tumor cells proved to be an effective cellular vaccine. However, the protective effect was lost in FcRI^–/– (but not in CD23^–/–) knockout mice, showing the IgE-FcRI interaction to be essential. Moreover, human IgE (not effective in BALB/c mice) had a protective effect in the humanized knockin mouse (FcRI^–/– hFcRI⁺). This finding suggests that the adjuvant effect of IgE could be exploited for human therapeutics.

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ This work was supported in part by the Ministero Italiano dell’Istruzione dell’Università e della Ricerca CoFin 2004 (to A.G.S.). E.A.N. was supported by a PhD fellowship from the University of Milan, Milan, Italy.

² Address correspondence and reprint requests to Dr. Luca Vangelista, San Raffaele Scientific Institute, Milan, Italy. E-mail address: vangelista.luca{at}hsr.it

³ Abbreviations used in this paper: TAA, tumor-associated Ag; DNFB, 2,4-dinitro-1-fluorobenzene; HER-2, human epidermal growth factor receptor 2; HSA, human serum albumin; VV, vaccinia virus; MVA, modified VV Ankara; WT, wild type.