与MOv18 IgE相关的非过敏性荨麻疹皮肤反应，MOv18 IgE是一种识别叶酸受体α的首创IgE抗体。
Non-Allergic Urticarial Skin Reactions Associated With MOv18 IgE, a First-In-Class IgE Antibody Recognising Folate Receptor Alpha.
作者信息
Stavraka Chara, Chauhan Jitesh, Crescioli Silvia, McSweeney Sheila M, Pope Amy, Gillett Cheryl, Di Meo Ashley, Prassas Ioannis, Laddach Roman, Stoker Katie, McCraw Alexandra J, Adams Rebecca, Tull Thomas J, Naban Nabeel, Willsmore Zena, Semkova Kristina V, Grattan Clive E H, McGrath John, Till Stephen J, Corrigan Christopher J, Kristeleit Rebecca, Tsoka Sophia, Diamandis Eleftherios P, Lacy Katie E, Pinder Sarah, Josephs Debra H, Spicer James, Bax Heather J, Karagiannis Sophia N
机构信息
St. John's Institute of Dermatology, School of Basic & Medical Biosciences & KHP Centre for Translational Medicine, King's College London, London, UK.
School of Cancer & Pharmaceutical Sciences, King's College London, Guy's Hospital, London, UK.
出版信息
Allergy. 2025 Mar 6. doi: 10.1111/all.16514.
BACKGROUND
IgE antibodies directed against cancer antigens have demonstrated potent anti-tumour effects in pre-clinical studies. MOv18 IgE, the first-in-class IgE recognising the cancer antigen folate receptor alpha (FRα), showed preliminary signs of efficacy in a Phase I trial. Treatment was well tolerated, with the most common adverse event being transient urticarial skin reactions. We investigated immunological and allergic response parameters associated with urticarial skin reactions in MOv18 IgE-treated patients.
METHODS
Expression of target antigen, FRα, and MOv18 IgE reactivity with FRα or any component in human skin was studied by immunohistochemistry, immunofluorescence and immuno-mass spectrometry. We conducted transcriptomic analyses in paired lesional and non-lesional skin biopsies from a patient who developed an urticarial skin reaction. Systemic immunological markers including cytokines, β-tryptase and basophil activation states were interrogated throughout the trial and contemporaneously with the skin reaction.
RESULTS
Of the 24 IgE-treated patients, 62.5% developed transient urticarial skin reactions, with onset during the first infusion, diminishing with consecutive infusions and no β-tryptase elevation nor clinical features indicating allergic aetiology. No FRα expression or MOv18 IgE binding to human skin was identified. Lesional skin biopsies from a patient given the highest antibody dose revealed scattered eosinophils, neutrophils and mast cell degranulation, but no increased immune cell infiltration. Transcriptomic analysis indicated pro-inflammatory, but not allergic, pathway activation. No systemic allergic or hypersensitivity mediators or basophil activation were detected.
CONCLUSIONS
Urticarial skin reactions following MOv18 IgE treatment were unlikely to result from allergic mechanisms or skin antigen recognition. The clinical presentation is consistent with infusion-related reactions commonly observed with monoclonal antibody treatments.
TRIAL REGISTRATION
EudraCT number: 2014-000070-19; ClinicalTrials.gov identifier: NCT02546921, registered 11/Sept/2015.
背景
在临床前研究中，针对癌症抗原的IgE抗体已显示出强大的抗肿瘤作用。MOv18 IgE是首个识别癌症抗原叶酸受体α（FRα）的IgE，在一项I期试验中显示出初步疗效迹象。治疗耐受性良好，最常见的不良事件是短暂性荨麻疹皮肤反应。我们研究了MOv18 IgE治疗患者中与荨麻疹皮肤反应相关的免疫和过敏反应参数。
方法
通过免疫组织化学、免疫荧光和免疫质谱研究了靶抗原FRα的表达以及MOv18 IgE与FRα或人皮肤中任何成分的反应性。我们对一名出现荨麻疹皮肤反应的患者的配对病变和非病变皮肤活检进行了转录组分析。在整个试验过程中以及与皮肤反应同时，检测了包括细胞因子、β-色氨酸酶和嗜碱性粒细胞激活状态在内的全身免疫标志物。
结果
在24名接受IgE治疗的患者中，62.5%出现了短暂性荨麻疹皮肤反应，在首次输注期间发作，随着连续输注而减轻，且β-色氨酸酶没有升高，也没有表明过敏病因的临床特征。未发现FRα表达或MOv18 IgE与人皮肤结合。给予最高抗体剂量的患者的病变皮肤活检显示有散在的嗜酸性粒细胞、中性粒细胞和肥大细胞脱颗粒，但免疫细胞浸润没有增加。转录组分析表明是促炎途径激活，而非过敏途径激活。未检测到全身过敏或超敏介质或嗜碱性粒细胞激活。
结论
MOv18 IgE治疗后出现的荨麻疹皮肤反应不太可能由过敏机制或皮肤抗原识别引起。临床表现与单克隆抗体治疗中常见的输注相关反应一致。
试验注册
欧洲药品管理局临床试验编号：2014-000070-19；ClinicalTrials.gov标识符：NCT02546921，于2015年9月11日注册。
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