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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Adenocarcinoma / immunology
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Adenocarcinoma / pathology
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Adenocarcinoma / therapy
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Adjuvants, Immunologic / metabolism
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Adjuvants, Immunologic / physiology*
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Adjuvants, Immunologic / therapeutic use*
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Animals
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Antigens, Neoplasm / immunology
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Antineoplastic Agents / administration & dosage
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Antineoplastic Agents / therapeutic use*
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Cancer Vaccines / administration & dosage
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Cancer Vaccines / genetics
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Cancer Vaccines / immunology
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Cell Line, Tumor
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Cross-Linking Reagents / administration & dosage
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Cross-Linking Reagents / metabolism
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Cross-Linking Reagents / therapeutic use
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Female
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Gene Knock-In Techniques
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Humans
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Immunoglobulin E / metabolism
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Immunoglobulin E / physiology*
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Immunoglobulin E / therapeutic use*
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Leukemia, Basophilic, Acute / immunology
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Leukemia, Basophilic, Acute / pathology
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Leukemia, Basophilic, Acute / therapy
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Lymphoma, T-Cell / immunology
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Lymphoma, T-Cell / pathology
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Lymphoma, T-Cell / therapy
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Mammary Neoplasms, Experimental / immunology
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Mammary Neoplasms, Experimental / pathology
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Mammary Neoplasms, Experimental / therapy
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Mice
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Mice, Inbred BALB C
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Mice, Inbred C57BL
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Mice, Knockout
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Mice, Transgenic
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Rats
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Receptors, IgE / deficiency
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Receptors, IgE / genetics
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Receptors, IgE / physiology*
Substances
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Adjuvants, Immunologic
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Antigens, Neoplasm
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Antineoplastic Agents
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Cancer Vaccines
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Cross-Linking Reagents
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Receptors, IgE
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Immunoglobulin E