Anti-lgE Monoclonal Antibodies that Inhibit Allergen-Specific Histamine Release

Shields, Robert L.; Werther, Winifred R.; Zioncheck, Kimberly; O’Connell, Lori; Klassen, Toni; Fendly, Brian M.; Presta, Leonard G.; Jardieu, Paula

doi:10.1159/000237058

Cited by 27 publications

(9 citation statements)

References 2 publications

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“…It forms complexes with circulating free IgE and prevents the binding of IgE to the high-and low-affinity receptors on cell membranes. It, therefore, impedes the recognition of the allergen by the effector cells such as mast cells, eosinophils, macrophages and dendritic cells, and inhibits their allergen-induced activation [23][24][25]. The antibody does not bind to cell-bound IgE and, therefore, does not trigger cell activation by crosslinking of the IgE molecules on cell membranes.…”

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confidence: 99%

The anti-IgE antibody omalizumab reduces exacerbations and steroid requirement in allergic asthmatics

et al. 2001

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The clinical benefit and steroid-sparing effect of treatment with the antiimmunoglobulin-E (IgE) antibody, omalizumab, was assessed in patients with moderateto-severe allergic asthma.After a run-in period, 546 allergic asthmatics (aged 12-76 yrs), symptomatic despite inhaled corticosteroids (500-1,200 mg daily of beclomethasone dipropionate), were randomized to receive double-blind either placebo or omalizumab every 2 or 4 weeks (depending on body weight and serum total IgE) subcutaneously for 7 months. A constant beclomethasone dose was maintained during a 16-week stable-steroid phase and progressively reduced to the lowest dose required for asthma control over the following 8 weeks. The latter dose was maintained for the next 4 weeks. Asthma exacerbations represented the primary variable.Compared to the placebo group, the omalizumab group showed 58% fewer exacerbations per patient during the stable-steroid phase (pv0.001). During the steroid-reduction phase, there were 52% fewer exacerbations in the omalizumab group versus the placebo group (pv0.001) despite the greater reduction of the beclomethasone dosage on omalizumab (pv0.001). Treatment with omalizumab was well tolerated. The incidence of adverse events was similar in both groups.These results indicate that omalizumab therapy safely improves asthma control in allergic asthmatics who remain symptomatic despite regular use of inhaled corticosteroids and simultaneous reduction in corticosteroid requirement.

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The anti-IgE antibody omalizumab reduces exacerbations and steroid requirement in allergic asthmatics

et al. 2001

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“…This antibody forms complexes with free (unbound) IgE but not with IgG or IgA. It blocks the binding of IgE to cell-membrane receptors, thereby inhibiting the release of receptors, but it does not bind to cell-bound IgE [9]. For clinical use, the amino acid residues of the variable immunoglobulin regions of mouse origin that were implicated in the binding of human IgG1 resulted in an immunoglobulin protein that is more than 95% human.…”

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confidence: 99%

Rat Monoclonal Anti-Murine IgE Antibody Removes IgE Molecules Already Bound to Mast Cells or Basophilic Leukemia Cells, Resulting in the Inhibition of Systemic Anaphylaxis and Passive Cutaneous Anaphylaxis

Miyajima

Watanabe²,

Óváry³

et al. 2002

Int Arch Allergy Immunol

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IgE plays a central role in allergic reactions. Some anti-IgE antibodies (HMK-12, 6HD5) inhibit the binding of IgE to the FcΕRI of mast cells/basophilic leukemia cells (PT-18, RBL/2H3), but less inhibition is seen with the anti-allotypic JKS-6 and the anti-idiotypic Eb-1. Anti-IgE HMK-12 can detach bound IgE molecules from the FcΕRI. When mast cells or basophils were incubated with monoclonal anti-DNP-IgE SPE-7, washed and treated with anti-IgE HMK-12, anti-IgE/IgE complexes were found in the supernatant. Similar results were obtained with the Fab fragment of HMK-12. Mice injected with anti-DNP-IgE SPE-7 and later with DNP-BSA had the typical systemic anaphylactic shock. However, if they were injected with the anti-IgE antibody (HMK-12) before the challenge, they did not get an anaphylactic shock. In the sera of mice injected with monoclonal IgE SPE-7 and anti-IgE antibody (HMK-12), IgE/anti-IgE complexes were detected. No passive cutaneous anaphylaxis occurred if the rats were injected with anti-IgE antibodies before the challenge. In summary, anti-IgE antibodies can remove IgE antibodies from the FcΕRI; anti-IgE/IgE complexes can be detected in vitro and in vivo, and anti-IgE antibodies can inhibit IgE-mediated systemic or local anaphylactic reactions.

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“…2,3 For example, omalizumab is a humanized antibody that binds to IgE and thereby sterically hinders its binding to FcεRI. [4][5][6][7] Omalizumab suppresses allergen-mediated degranulation of mast cells and basophils without stimulating the IgE-mediated cross-linking of FcεRI on these cell types. Notably, the therapeutic activity of omalizumab does not involve the suppression of IgE 1 B cells or a decrease in the continuous production of allergen-specific IgE by plasma cells, 8 although IgE sequestration may trigger indirect effects including downregulation of FcεRI expression.…”

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confidence: 99%

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

Chu¹,

Horton²,

Pong

et al. 2012

Journal of Allergy and Clinical Immunology

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Anti-lgE Monoclonal Antibodies that Inhibit Allergen-Specific Histamine Release

Cited by 27 publications

References 2 publications

The anti-IgE antibody omalizumab reduces exacerbations and steroid requirement in allergic asthmatics

The anti-IgE antibody omalizumab reduces exacerbations and steroid requirement in allergic asthmatics

Rat Monoclonal Anti-Murine IgE Antibody Removes IgE Molecules Already Bound to Mast Cells or Basophilic Leukemia Cells, Resulting in the Inhibition of Systemic Anaphylaxis and Passive Cutaneous Anaphylaxis

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

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