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 Fc(epsilon)RIalpha(-/-) (but not in CD23(-/-)) knockout mice, showing the IgE-Fc(epsilo)nRI interaction to be essential. Moreover, human IgE (not effective in BALB/c mice) had a protective effect in the humanized knockin mouse (Fc(epsilon)RIalpha(-/-) hFc(epsilon)RIalpha(+)). This finding suggests that the adjuvant effect of IgE could be exploited for human therapeutics.

Antitumor IgE adjuvanticity: Key role of FcεRI

AMBROSI , ALESSANDRO;
2009

Abstract

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 Fc(epsilon)RIalpha(-/-) (but not in CD23(-/-)) knockout mice, showing the IgE-Fc(epsilo)nRI interaction to be essential. Moreover, human IgE (not effective in BALB/c mice) had a protective effect in the humanized knockin mouse (Fc(epsilon)RIalpha(-/-) hFc(epsilon)RIalpha(+)). This finding suggests that the adjuvant effect of IgE could be exploited for human therapeutics.
ANTIBODY-DEPENDENT CYTOTOXICITY; ACUTE LYMPHOBLASTIC-LEUKEMIA; OVARIAN TUMOR-CELLS; PANCREATIC-CANCER; RECEPTOR; ALLERGIES; CARCINOMA; HISTORY; GROWTH; ASSOCIATION
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/20.500.11768/139
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