O19 Nonallergic urticarial skin reactions associated with MOv18 IgE, a first-in-class IgE antibody recognizing folate receptor alpha (FRα): linking allergooncology with dermatology

Abstract Introduction and aims IgE class antibodies directed against cancer antigens can activate tumour-infiltrating immune cells to restrict cancer growth. MOv18, the first-in-class IgE recognizing the cancer antigen folate receptor (FR)α demonstrated early signs of efficacy in a phase I clinical trial. The most common toxicity was transient urticarial skin reactions. We investigated the immunological and allergic basis of these skin reactions. Methods Twenty-four patients with FRα-positive tumours received escalating doses of MOv18 IgE. Clinical data regarding urticarial skin reactions were collected. We studied expression of the target antigen, FRα, in human skin, reactivity of MOv18 with human skin by immunohistochemistry (IHC), immunofluorescence and immuno-mass spectrometry (IMS). We conducted transcriptomic analyses in paired lesional and nonlesional skin biopsies from an affected patient. Circulating immunological markers including cytokines, β-tryptase and basophil activation states were interrogated throughout treatment, including contemporaneously with any skin reaction to evaluate links to systemic allergic responses. Results Urticarial reactions occurred in 62.5% of patients, were mostly mild and diminishing with repeated doses. These reactions were not associated with serum β-tryptase elevation, indicating an absence of systemic allergic activity. Using IHC and IMS we confirmed FRα is not expressed in normal skin and MOv18 IgE did not bind to skin antigens. Urticarial skin biopsies from a patient showed scattered eosinophils, neutrophils and mast cell degranulation without increased immune cell infiltration. Transcriptomic analysis indicated activation of proinflammatory but not allergic pathways, with no cytokine markers of allergic hypersensitivity or basophil activation detected in circulation. Conclusions Urticarial skin reactions in MOv18 IgE-treated patients were not driven by allergic mechanisms or antibody-skin antigen recognition, and likely represent infusion-related phenomena common with monoclonal antibody therapies. These findings affirm the safety of MOv18 IgE, with manageable reactions, and provide key insights for advancing IgE-based cancer immunotherapy while prioritising patient safety.