Active Induction of Tumor-Specific IgE Antibodies by Oral Mimotope Vaccination

Riemer, Angelika B.; Untersmayr, Eva; Knittelfelder, Regina; Duschl, Albert; Pehamberger, Hubert; Zielinski, Christoph; Scheiner, Otto; Jensen‐Jarolim, Erika

doi:10.1158/0008-5472.can-06-3758

Cited by 41 publications

(31 citation statements)

References 43 publications

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“…Oral immunization of mice with mimotopes of trastuzumab, an anti-human epidermal growth factor receptor (HER)-2 mAb, led to the development of HER-2-specific IgE. HER-2-specific IgE-bound tumor cells could be killed in vitro by FcRI ϩ effector cells (24). Our first approach in the study of an IgE-mediated immune response in the prevention and control of tumor growth relied on the in vitro or in vivo targeting of IgE on the surface of tumor cells by a three-step strategy (25).…”

mentioning

confidence: 99%

Antitumor IgE Adjuvanticity: Key Role of FcεRI

Nigro

Brini

Soprana

et al. 2009

The Journal of Immunology

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

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confidence: 99%

Antitumor IgE Adjuvanticity: Key Role of FcεRI

Nigro

Brini

Soprana

et al. 2009

The Journal of Immunology

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“…Jensen-Jarolim et al (33) showed that oral vaccination with a breast tumor "Ag" stimulates the production of IgE Abs that activate IgE effector cells and mediate tumor cell lysis in vitro. Reali et al (34) have shown that passive immunization with IgE Abs can also result in stimulating an active immune response.…”

mentioning

confidence: 99%

IgE-Antibody-Dependent Immunotherapy of Solid Tumors: Cytotoxic and Phagocytic Mechanisms of Eradication of Ovarian Cancer Cells

Karagiannis

Bracher

Hunt

et al. 2007

The Journal of Immunology

100

124

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Abs have a paramount place in the treatment of certain, mainly lymphoid, malignancies, although tumors of nonhemopoietic origin have proved more refractory ones. We have previously shown that the efficacy of immunotherapy of solid tumors, in particular ovarian carcinoma, may be improved by the use of IgE Abs in place of the conventional IgG. An IgE Ab (MOv18 IgE) against an ovarian-tumor-specific Ag (folate binding protein), in combination with human PBMC, introduced into ovarian cancer xenograft-bearing mice, greatly exceeded the analogous IgG1 in promoting survival. In this study, we analyzed the mechanisms by which MOv18 IgE may exert its antitumor activities. Monocytes were essential IgE receptor-expressing effector cells that mediated the enhanced survival of tumor-bearing mice by MOv18 IgE and human PBMC. Monocytes mediated MOv18 IgE-dependent ovarian tumor cell killing in vitro by two distinct pathways, cytotoxicity and phagocytosis, acting respectively through the IgE receptors FcεRI and CD23. We also show that human eosinophils were potent effector cells in MOv18 IgE Ab-dependent ovarian tumor cell cytotoxicity in vitro. These results demonstrate that IgE Abs can engage cell surface IgE receptors and activate effector cells against ovarian tumor cells. Our findings offer a framework for an improved immunotherapeutic strategy for combating solid tumors.

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“…A number of groups have examined the concept of raising IgE antibodies through a number of active immunization approaches and also by harnessing powerful immune effector cell functions against cancer cells through passive immunotherapy with monoclonal antibodies (138,139,140,142,146,147,148,149,150,151,152,153). A growing number of studies, including those from our group, demonstrate the promise of activating allergic responses against cancer and have defined the emerging field of AllergoOncology (138,154,155).…”

Section: Concluding Remarks and Future Roles Of Antibodies In Therapymentioning

confidence: 99%

Immunoglobulin E and Allergy: Antibodies in Immune Inflammation and Treatment

Karagiannis

Josephs

et al. 2013

Microbiol Spectr

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The pathogenic role of immunoglobulin E (IgE) antibodies in triggering and maintaining allergic inflammation in response to allergens is due to the binding of multivalent allergens to allergen-specific IgEs on sensitized effector cells. These interactions trigger effector cell activation, resulting in release of potent inflammatory mediators, recruitment of inflammatory cells, antigen presentation, and production of allergen-specific antibody responses. Since its discovery in the 1960s, the central role of IgE in allergic disease has been intensively studied, placing IgE and its functions at the heart of therapeutic efforts for the treatment of allergies. Here, we provide an overview of the nature, roles, and significance of IgE antibodies in allergic diseases, infections, and inflammation and the utility of antibodies as therapies. We place special emphasis on allergen-IgEFcε receptor complexes in the context of allergic and inflammatory diseases and describe strategies, including monoclonal antibodies, aimed at interrupting these complexes. Of clinical significance, one antibody, omalizumab, is presently in clinical use and works by preventing formation of IgE-Fcε receptor interactions. Active immunotherapy approaches with allergens and allergen derivatives have also demonstrated clinical benefits for patients with allergic diseases. These treatments are strongly associated with serum increases of IgE-neutralizing antibodies and feature a notable redirection of humoral responses towards production of antibodies of the IgG4 subclass in patients receiving immunotherapies. Lastly, we provide a new perspective on the rise of recombinant antibodies of the IgE class recognizing tumor-associated antigens, and we discuss the potential utility of tumor antigen-specific IgE antibodies to direct potent IgE-driven immune responses against tumors.

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Active Induction of Tumor-Specific IgE Antibodies by Oral Mimotope Vaccination

Cited by 41 publications

References 43 publications

Antitumor IgE Adjuvanticity: Key Role of FcεRI

Antitumor IgE Adjuvanticity: Key Role of FcεRI

IgE-Antibody-Dependent Immunotherapy of Solid Tumors: Cytotoxic and Phagocytic Mechanisms of Eradication of Ovarian Cancer Cells

Immunoglobulin E and Allergy: Antibodies in Immune Inflammation and Treatment

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