Omalizumab是一种针对人免疫球蛋白E（IgE）的重组人源化单克隆抗体，KD值为0.393nM。
Cas No.:242138-07-4
Sample solution is provided at 25 µL, 10mM.
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Omalizumab is a recombinant humanized monoclonal antibody against human immunoglobulin E (IgE) with a KD value of 0.393nM[1]. Omalizumab is a human IgG1 kappa antibody that binds with high specificity to free IgE, which is widely present in human blood and tissue fluid[2]. Omalizumab inhibits the binding of IgE to FcεRI on mast cells and basophils by binding to an antigenic epitope on IgE that overlaps with the binding site of FcεRI[3]. Omalizumab can be used to treat severe persistent allergic asthma, nasal polyps, urticaria, and IgE-mediated food allergies[4, 5].
In vitro, treatment of human mast cell line (LAD2 cells) and basophils with Omalizumab (30, 100, 300µg/mL) for 24h promoted the dissociation of IgE bound to the surface of mast cells and basophils, inhibited key signaling events mediated by proximal phosphorylation (such as activation of Syk, PLCγ, and LAT), and reduced cell degranulation and leukotriene synthesis[6].
In vivo, subcutaneous treatment of an asthmatic model of cynomolgus monkeys with Omalizumab (10mg/kg) for 3 weeks significantly reduced airway resistance (RL) and lung dynamic compliance (Cdyn)[7].
References:
[1] Chu S Y, Horton H M, Pong E, et al. Reduction of total IgE by targeted coengagement of IgE B-cell receptor and FcγRIIb with Fc-engineered antibody[J]. Journal of allergy and clinical immunology, 2012, 129(4): 1102-1115.
[2] Lyly A, Laulajainen-Hongisto A, Gevaert P, et al. Monoclonal antibodies and airway diseases[J]. International Journal of Molecular Sciences, 2020, 21(24): 9477.
[3] Gomez G. Current strategies to inhibit high affinity FcεRI-mediated signaling for the treatment of allergic disease[J]. Frontiers in immunology, 2019, 10: 175.
[4] McCormack P L. Omalizumab: a review of its use in patients with chronic spontaneous urticaria[J]. Drugs, 2014, 74(14): 1693-1699.
[5] Wood R A, Togias A, Sicherer S H, et al. Omalizumab for the treatment of multiple food allergies[J]. New England Journal of Medicine, 2024, 390(10): 889-899.
[6] Serrano‐Candelas E, Martinez‐Aranguren R, Valero A, et al. Comparable actions of omalizumab on mast cells and basophils[J]. Clinical & Experimental Allergy, 2016, 46(1): 92-102.
[7] Liu P, Pan Z, Gu C, et al. An omalizumab biobetter antibody with improved stability and efficacy for the treatment of allergic diseases[J]. Frontiers in immunology, 2020, 11: 596908.
Omalizumab是一种针对人免疫球蛋白E（IgE）的重组人源化单克隆抗体，KD值为0.393nM[1]。Omalizumab属于Human IgG1 kappa，能够高特异性地结合人体血液和组织液中广泛存在的游离IgE[2]。Omalizumab通过与IgE上的抗原表位结合，该表位与FcεRI结合的位点重叠，从而抑制IgE与肥大细胞和嗜碱性粒细胞上的FcεRI结合[3]。Omalizumab能够用于治疗严重的持续性过敏性哮喘、鼻息肉、荨麻疹和IgE介导的食物过敏[4, 5]。
在体外，Omalizumab（30, 100, 300µg/mL）处理人肥大细胞系（LAD2细胞）和嗜碱性粒细胞24h，能够促使已结合在肥大细胞和嗜碱性粒细胞表面的IgE解离，抑制了由近端磷酸化介导的关键信号事件（如Syk、PLCγ和LAT的激活），减少了细胞的脱颗粒反应和白三烯合成[6]。
在体内，Omalizumab（10mg/kg）通过皮下注射治疗哮喘模型食蟹猴3周，显著降低了食蟹猴的气道阻力（RL）和肺动态顺应性（Cdyn）[7]。
| Cell experiment [1]: | |
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Cell lines |
LAD2 cells |
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Preparation Method |
LAD2 cells were sensitized overnight with IgEB (100 ng/mL) in culture media. The following day, the cells were washed three times in Tyrode’s buffer to eliminate unbound IgE, were subsequently incubated with Omalizumab or hIgG at different concentrations (high-dose experiments: 2, 1, 0.5, and 0.25mg/mL; or low-dose experiments: 300, 100 and 30µg/mL) in culture media and for different periods of time (30min, 3h, 24h), and were then stimulated with streptavidin for varying periods of time. Supernatants were collected for CysLT measurement, and the cells were used for WB analysis or FACS staining. |
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Reaction Conditions |
0.25, 0.5, 1, 2mg/mL or 30, 100, 300µg/mL; 30min, 3h, 24h |
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Applications |
Omalizumab dissociates pre-bound IgE from mast cells, resulting in a reduction of proximal phosphorylation-mediated signalling events (Syk, PLCγ, and LAT) and in a decrease in degranulation and leukotriene synthesis. |
| Animal experiment [2]: | |
|
Animal models |
Cynomolgus monkeys |
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Preparation Method |
3-7 years old male cynomolgus monkeys weighing between 3 and 7 kg were used. To develop the allergic asthma models, monkeys were sensitized with dinitrophenyl-Ascaris suum (DNP-As) allergen. After modeling, monkeys received a dose of 10mg/kg test antibody (AB1904Am15) once a week via subcutaneous administration for 3 weeks. Humanized IgG1 antibody was used as isotype control. Omalizumab was used as a positive control. Airway resistance (RL) and lung dynamic compliance (Cdyn) were measured at 24h post 1st and 3rd dosing. |
|
Dosage form |
10mg/kg; 3 weeks; s.c. |
|
Applications |
Monkeys treated with AB1904Am15 or Omalizumab showed significant decreases in RL and Cdyn at 24 hours after the first and third doses, compared to the isotype control group. |
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References: |
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| Cas No. | 242138-07-4 | SDF | |
| 别名 | 奥马珠单抗; Olizumab; rhuMab-E25 | ||
| 分子式 | C6450H9916N1714O2023S38 | 分子量 | 145056.09 |
| 溶解度 | 储存条件 | Store at -80°C | |
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| 制备储备液 | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 6.9 μL | 34.5 μL | 68.9 μL |
| 5 mM | 1.4 μL | 6.9 μL | 13.8 μL |
| 10 mM | 0.7 μL | 3.4 μL | 6.9 μL |
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| 给药剂量 | mg/kg |  |
动物平均体重 | g | |
每只动物给药体积 | ul | |
动物数量 | 只 |
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| % DMSO % % Tween 80 % saline | ||||||||||
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计算结果:
工作液浓度： mg/ml；
DMSO母液配制方法： mg 药物溶于 μL DMSO溶液（母液浓度 mg/mL，
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2.
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Purity: >98.00%
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