Reduction of total IgE by targeted coengagement of IgE B-cell receptor and FcγRIIb with Fc-engineered antibody

Chu, Seung Y.; Horton, Holly M.; Pong, Erik; Leung, Irene; Chen, Hsing; Nguyen, Duc-Hanh T.; Bautista, Cristina; Muchhal, Umesh S.; Bernett, Matthew J.; Moore, Gregory L.; Szymkowski, David E.; Desjarlais, John R.

doi:10.1016/j.jaci.2011.11.029

Cited by 79 publications

(83 citation statements)

References 35 publications

(57 reference statements)

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“…However, there is also another potential explanation: Omalizumab may cross-link IgE present on the surface of IgE-positive memory B cells as B cell receptors by binding to its Cε3-free regions [6,7]. These memory cells could be thereby activated, resulting in enhanced IgE production and total serum IgE levels.…”

mentioning

confidence: 99%

Omalizumab's Impact on Total and Allergen-Specific IgE Levels: A Polyclonal Story

Eckl‐Dorna

2016

Int Arch Allergy Immunol

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confidence: 99%

Omalizumab's Impact on Total and Allergen-Specific IgE Levels: A Polyclonal Story

Eckl‐Dorna

2016

Int Arch Allergy Immunol

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“…The first possibility is based on findings that the administration of anti‐IgE antibodies into primed mice16 as well as injection of oligomeric allergen derivatives17 which are able to cross‐link the BCR on IgE‐producing memory cells into sensitized mice can boost secondary IgE production. This hypothesis has been controversially discussed with arguments in favour14, 16, 32, 33 and against34, 35 the potential of omalizumab to activate IgE + memory B cells. In the present study, both in our in vivo intranasal challenge model and in our in vitro approach using a well‐established system to induce IgE production,30, 31 we did not observe any enhancing effect of omalizumab on IgE production.…”

Section: Discussionmentioning

confidence: 99%

Intranasal administration of allergen increases specific IgE whereas intranasal omalizumab does not increase serum IgE levels—A pilot study

Eckl‐Dorna

Fröschl

Lupinek

et al. 2017

Allergy

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BackgroundAdministration of the therapeutic anti‐IgE antibody omalizumab to patients induces strong increases in IgE antibody levels.ObjectiveTo investigate the effect of intranasal administration of major birch pollen allergen Bet v 1, omalizumab or placebo on the levels of total and allergen‐specific IgE in patients with birch pollen allergy.MethodsBased on the fact that intranasal allergen application induces rises of systemic allergen‐specific IgE, we performed a double‐blind placebo‐controlled pilot trial in which birch pollen allergic subjects were challenged intranasally with omalizumab, placebo or birch pollen allergen Bet v 1. Total and allergen‐specific IgE, IgG and basophil sensitivity were measured before and 8 weeks after challenge. For control purposes, total, allergen‐specific IgE levels and omalizumab‐IgE complexes as well as specific IgG levels were studied in subjects treated subcutaneously with either omalizumab or placebo. Effects of omalizumab on IgE production by IL‐4/anti‐CD40‐treated PBMCs from allergic patients were studied in vitro.ResultsIntranasal challenge with Bet v 1 induced increases in Bet v 1‐specific IgE levels by a median of 59.2%, and this change differed significantly from the other treatment groups (P = .016). No relevant change in allergen‐specific and total IgE levels was observed in subjects challenged with omalizumab. Addition of omalizumab did not enhance IL‐4/anti‐CD40‐induced IgE production in vitro. Significant rises in total IgE (mean IgE before: 131.83 kU/L to mean IgE after: 505.23 kU/L) and the presence of IgE‐omalizumab complexes were observed after subcutaneous administration of omalizumab.ConclusionIntranasal administration of allergen induced rises of allergen‐specific IgE levels, whereas intranasal administration of omalizumab did not enhance systemic total or allergen‐specific IgE levels.

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“…Another approach encompasses an anti-IgE antibody, XmAb7195, with modified IgG Fc domains that feature increased affinity to the inhibitory FcγRIIB expressed on B cells and also the ability to suppress B-cell activation. Like omalizumab, this agent was recently reported to target the Cε3 domains of free IgE but to also cointeract with IgE in the complex with FcγRIIB on the surface of IgE-expressing B cells (99). This antibody was shown to suppress B-cell signaling and prevent maturation of B cells into IgE + plasma cells, reducing total IgE in circulation in vivo while neutralizing IgE in a manner similar to omalizumab.…”

Section: Antibodies Blocking Cd23 Functions and B Cellsmentioning

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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Reduction of total IgE by targeted coengagement of IgE B-cell receptor and FcγRIIb with Fc-engineered antibody

Cited by 79 publications

References 35 publications

Omalizumab's Impact on Total and Allergen-Specific IgE Levels: A Polyclonal Story

Omalizumab's Impact on Total and Allergen-Specific IgE Levels: A Polyclonal Story

Intranasal administration of allergen increases specific IgE whereas intranasal omalizumab does not increase serum IgE levels—A pilot study

Immunoglobulin E and Allergy: Antibodies in Immune Inflammation and Treatment

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