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

Chara Stavraka; Jitesh Chauhan; Silvia Crescioli; Sheila M McSweeney; Amy Pope; Cheryl Gillett; Ashley Di Meo; Ioannis Prassas; Roman Laddach; Katie Stoker; Alexandra J McCraw; Rebecca Adams; Thomas J Tull; Nabeel Naban; Zena Willsmore; Kristina V Semkova; Clive E H Grattan; John McGrath; Stephen J Till; Christopher J Corrigan; Rebecca Kristeleit; Sophia Tsoka; Eleftherios P Diamandis; Katie E Lacy; Sarah Pinder; Debra H Josephs; James Spicer; Heather J Bax; Sophia N Karagiannis

doi:10.1111/all.16514

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

Chara Stavraka, Jitesh Chauhan, Silvia Crescioli, Sheila M McSweeney, Amy Pope, Cheryl Gillett, Ashley Di Meo, Ioannis Prassas, Roman Laddach, Katie Stoker, Alexandra J McCraw, Rebecca Adams, Thomas J Tull, Nabeel Naban, Zena Willsmore, Kristina V Semkova, Clive E H Grattan, John McGrath, Stephen J Till, Christopher J CorriganRebecca Kristeleit, Sophia Tsoka, Eleftherios P Diamandis, Katie E Lacy, Sarah Pinder, Debra H Josephs, James Spicer, Heather J Bax, Sophia N Karagiannis

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Abstract

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.

Original language	English
Number of pages	15
Journal	Allergy
DOIs	https://doi.org/10.1111/all.16514
Publication status	E-pub ahead of print - 6 Mar 2025

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10.1111/all.16514Licence: CC BY

Stavraka Chauhan et al Allergy 2025 100176460Final published version, 4.49 MBLicence: CC BY

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Stavraka, C., Chauhan, J., Crescioli, S., McSweeney, S. M., Pope, A., Gillett, C., Di Meo, A., Prassas, I., Laddach, R., Stoker, K., McCraw, A. J., Adams, R., Tull, T. J., Naban, N., Willsmore, Z., Semkova, K. V., Grattan, C. E. H., McGrath, J., Till, S. J., ... Karagiannis, S. N. (2025). Non-Allergic Urticarial Skin Reactions Associated With MOv18 IgE, a First-In-Class IgE Antibody Recognising Folate Receptor Alpha. Allergy. Advance online publication. https://doi.org/10.1111/all.16514

@article{4b612cf7655047589b34d6fce94b51f4,

title = "Non-Allergic Urticarial Skin Reactions Associated With MOv18 IgE, a First-In-Class IgE Antibody Recognising Folate Receptor Alpha",

abstract = "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.",

author = "Chara Stavraka and Jitesh Chauhan and Silvia Crescioli and McSweeney, {Sheila M} and Amy Pope and Cheryl Gillett and {Di Meo}, Ashley and Ioannis Prassas and Roman Laddach and Katie Stoker and McCraw, {Alexandra J} and Rebecca Adams and Tull, {Thomas J} and Nabeel Naban and Zena Willsmore and Semkova, {Kristina V} and Grattan, {Clive E H} and John McGrath and Till, {Stephen J} and Corrigan, {Christopher J} and Rebecca Kristeleit and Sophia Tsoka and Diamandis, {Eleftherios P} and Lacy, {Katie E} and Sarah Pinder and Josephs, {Debra H} and James Spicer and Bax, {Heather J} and Karagiannis, {Sophia N}",

note = "Publisher Copyright: {\textcopyright} 2025 The Author(s). Allergy published by European Academy of Allergy and Clinical Immunology and John Wiley & Sons Ltd.",

year = "2025",

month = mar,

day = "6",

doi = "10.1111/all.16514",

language = "English",

journal = "Allergy",

issn = "0105-4538",

publisher = "John Wiley and sons",

}

Stavraka, C , Chauhan, J , Crescioli, S , McSweeney, SM, Pope, A, Gillett, C, Di Meo, A, Prassas, I, Laddach, R , Stoker, K , McCraw, AJ , Adams, R , Tull, TJ, Naban, N, Willsmore, Z, Semkova, KV, Grattan, CEH, McGrath, J , Till, SJ , Corrigan, CJ , Kristeleit, R , Tsoka, S, Diamandis, EP, Lacy, KE, Pinder, S , Josephs, DH , Spicer, J , Bax, HJ & Karagiannis, SN 2025, 'Non-Allergic Urticarial Skin Reactions Associated With MOv18 IgE, a First-In-Class IgE Antibody Recognising Folate Receptor Alpha', Allergy. https://doi.org/10.1111/all.16514

TY - JOUR

T1 - Non-Allergic Urticarial Skin Reactions Associated With MOv18 IgE, a First-In-Class IgE Antibody Recognising Folate Receptor Alpha

AU - Stavraka, Chara

AU - Chauhan, Jitesh

AU - Crescioli, Silvia

AU - McSweeney, Sheila M

AU - Pope, Amy

AU - Gillett, Cheryl

AU - Di Meo, Ashley

AU - Prassas, Ioannis

AU - Laddach, Roman

AU - Stoker, Katie

AU - McCraw, Alexandra J

AU - Adams, Rebecca

AU - Tull, Thomas J

AU - Naban, Nabeel

AU - Willsmore, Zena

AU - Semkova, Kristina V

AU - Grattan, Clive E H

AU - McGrath, John

AU - Till, Stephen J

AU - Corrigan, Christopher J

AU - Kristeleit, Rebecca

AU - Tsoka, Sophia

AU - Diamandis, Eleftherios P

AU - Lacy, Katie E

AU - Pinder, Sarah

AU - Josephs, Debra H

AU - Spicer, James

AU - Bax, Heather J

AU - Karagiannis, Sophia N

PY - 2025/3/6

Y1 - 2025/3/6

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=86000316506&partnerID=8YFLogxK

U2 - 10.1111/all.16514

DO - 10.1111/all.16514

M3 - Article

C2 - 40045925

SN - 0105-4538

JO - Allergy

JF - Allergy

ER -

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

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