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.
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