Targeting IgE in allergic disease

Gasser, Philippe; Eggel, Alexander

doi:10.1016/j.coi.2018.05.015

Cited by 39 publications

(38 citation statements)

References 49 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…It could be speculated that this limited effect might be explained by the fact that omalizumab also inhibits IgE binding to CD23. 58 If CD23 is physiologically the noninflammatory IgE pathway, an anti-IgE antibody designed in a way that it reduces FcεRI binding but enhances CD23 targeting could potentially be more effective.…”

Section: Discussionmentioning

confidence: 99%

CD23 provides a noninflammatory pathway for IgE-allergen complexes

Engeroff

Caviezel

Mueller

et al. 2020

Journal of Allergy and Clinical Immunology

View full text Add to dashboard Cite

High affinity Low affinity Free IgE Allergen encounter Reduced binding IgE-allergen complex CD23 CD23 FcεRI FcεRI FcεRI CD23 provides a noninflammatory pathway for IgE-allergen complexes Inflammatory pathway Noninflammatory pathway Increased binding Background: Type I hypersensitivity is mediated by allergen-specific IgE, which sensitizes the high-affinity IgE receptor FcεRI on mast cells and basophils and drives allergic inflammation upon secondary allergen contact. CD23/FcεRII, the low-affinity receptor for IgE, is constitutively expressed on B cells and has been shown to

show abstract

Section: Discussionmentioning

confidence: 99%

CD23 provides a noninflammatory pathway for IgE-allergen complexes

Engeroff

Caviezel

Mueller

et al. 2020

Journal of Allergy and Clinical Immunology

View full text Add to dashboard Cite

show abstract

“…Ligelizumab is a humanized monoclonal IgG1 antibody that binds IgE with an affinity of ∼1.4 χ 10 −10 M but does not interact with FcεRIα-bound IgE. 22 dose-finding trial for CSU last year. 62 It was also superior to omalizumab in the inhibition of primary human basophil activation and a passive systemic anaphylaxis mouse model.…”

Section: Monoclonal Anti-ige Antibody Ligelizumabmentioning

confidence: 99%

Past, present, and future of anti‐IgE biologics

Guntern

Eggel

2020

Allergy

Self Cite

View full text Add to dashboard Cite

The discovery of immunoglobulin E (IgE) in 1967 1-9 together with the identification of its central role in the pathogenesis of allergic inflammation (reviewed elsewhere 10-14) has set the stage for the development of therapeutic anti-IgE strategies (Box 1). The generation of detailed knowledge about the molecular and structural characteristics of IgE has further accelerated this process. IgE consists of two identical heavy and light chains. Each heavy chain includes four constant epsilon domains (Cε1-4). 15 Overall, the IgE antibody features high flexibility. Particularly, the IgE-Fc part has been described to undergo important conformational changes depending on its interaction partner. While IgE binding to the high-affinity receptor FcεRI on allergic effector cells induces an open Fc conformation, low affinity receptor FcεRII/CD23 binding on antigen-presenting cells (APC), airway epithelial cells (AEC) or B-cells forces IgE in a closed Fc conformation and thereby ensures mutually exclusive interaction with the two receptors. 16-18 In addition to the free form of IgE, B cells express membrane IgE (mIgE) that is part of the B-cell receptor (BCR) and contains an extracellular membrane-proximal domain (EMPD). 19-21 Identification of these features has been key for the development of efficient targeting strategies. Over the last decades, the field of anti-IgE biologicals has advanced into a competitive and active field of investigation. Different companies and research institutions are currently assessing approaches to specifically target IgE in pre-clinical studies or clinical trials (Table 1). 22,23 Here, we provide

show abstract

“…A s a key driver in the development and manifestation of hypersensitivity reactions against normally nonhazardous substances, immunoglobulin E (IgE) has become a major target of therapeutic intervention strategies [1][2][3] . IgE is known to interact with two major receptors, FcεRI and CD23/FcεRII 4 , which are involved in different immunological processes 5 .…”

mentioning

confidence: 99%

The mechanistic and functional profile of the therapeutic anti-IgE antibody ligelizumab differs from omalizumab

et al. 2020

Self Cite

View full text Add to dashboard Cite

Targeting of immunoglobulin E (IgE) represents an interesting approach for the treatment of allergic disorders. A high-affinity monoclonal anti-IgE antibody, ligelizumab, has recently been developed to overcome some of the limitations associated with the clinical use of the therapeutic anti-IgE antibody, omalizumab. Here, we determine the molecular binding profile and functional modes-of-action of ligelizumab. We solve the crystal structure of ligelizumab bound to IgE, and report epitope differences between ligelizumab and omalizumab that contribute to their qualitatively distinct IgE-receptor inhibition profiles. While ligelizumab shows superior inhibition of IgE binding to FcεRI, basophil activation, IgE production by B cells and passive systemic anaphylaxis in an in vivo mouse model, ligelizumab is less potent in inhibiting IgE:CD23 interactions than omalizumab. Our data thus provide a structural and mechanistic foundation for understanding the efficient suppression of FcεRI-dependent allergic reactions by ligelizumab in vitro as well as in vivo.

show abstract

Targeting IgE in allergic disease

Cited by 39 publications

References 49 publications

CD23 provides a noninflammatory pathway for IgE-allergen complexes

CD23 provides a noninflammatory pathway for IgE-allergen complexes

Past, present, and future of anti‐IgE biologics

The mechanistic and functional profile of the therapeutic anti-IgE antibody ligelizumab differs from omalizumab

Contact Info

Product

Resources

About