Non-Allergic Urticarial Skin Reactions Associated With MOv18 IgE, a First-In-Class IgE Antibody Recognising Folate...

Area of Science:

• Immunology
• Oncology
• Dermatology

Background:

• IgE antibodies targeting cancer antigens show anti-tumor effects.
• MOv18 IgE targets folate receptor alpha (FRα) and showed preliminary efficacy in a Phase I trial.
• Urticarial skin reactions were the most common adverse event.

Purpose of the Study:

• Investigate immunological and allergic responses linked to urticarial skin reactions during MOv18 IgE treatment.
• Determine if FRα expression or MOv18 IgE binding in skin causes these reactions.
• Assess systemic markers for allergic or hypersensitivity reactions.

Main Methods:

• Immunohistochemistry, immunofluorescence, and immuno-mass spectrometry to assess FRα expression and IgE binding in skin.
• Transcriptomic analysis of lesional and non-lesional skin biopsies.
• Systemic analysis of cytokines, β-tryptase, and basophil activation.

Main Results:

• 62.5% of patients experienced transient urticarial skin reactions, primarily during the first infusion.
• No FRα expression or MOv18 IgE binding to human skin was detected.
• Skin biopsies showed inflammation but not allergic infiltration; systemic markers did not indicate allergic reactions.

Conclusions:

• Urticarial skin reactions to MOv18 IgE are unlikely due to allergic mechanisms or skin antigen recognition.
• The observed reactions are consistent with infusion-related responses typical of monoclonal antibody treatments.
• Further investigation into the mechanisms of these reactions is warranted.