Assessment of biophysical properties of the first-in-class anti-cancer IgE antibody drug, MOv18 IgE demonstrates monomeric purity and stability

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Considine, Paul and Punnabhum, Panida and Davidson, Callum G. and Armstrong, Georgina B. and Kreiner, Michaela and Bax, Heather J. and Chauhan, Jitesh and Spicer, James and Josephs, Debra H. and Karagiannis, Sophia N. and Halbert, Gavin and Rattray, Zahra (2025) Assessment of biophysical properties of the first-in-class anti-cancer IgE antibody drug, MOv18 IgE demonstrates monomeric purity and stability. mAbs, 17 (1). 2512211. (https://doi.org/10.1080/19420862.2025.2512211)

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Abstract

Therapeutic monoclonal antibodies, which are almost exclusively IgG isotypes, show significant promise but are prone to poor solution stability, including aggregation and elevated solution viscosity at dose-relevant concentrations. Recombinant IgE antibodies are emerging cancer immunotherapies. The first-in-class MOv18 IgE, recognizing the cancer-associated antigen Folate Receptor-alpha (FRα), completed a Phase I clinical trial in patients with solid tumours, showing early signs of efficacy at a low dose. The inaugural process development and scaled manufacture of MOv18 IgE for clinical testing was undertaken with little baseline knowledge about the solution phase behaviour of recombinant IgE at dose-relevant concentrations. We evaluated MOv18 IgE physical stability in response to environmental and formulation stresses encountered throughout shelf life. We analysed changes in physical stability using multiple orthogonal analytical techniques, including, particle tracking analysis, size exclusion chromatography, and multidetector flow field flow fractionation hyphenated with UV. We used dynamic and multiangle light scattering to profile aggregation status. Formulation at pH 6.5, selected for use in the Phase I trial, resulted in high monomeric purity and no submicron proteinaceous particulates. Formulation at pH 5.5 and 7.5 induced significant submicron and sub-visible particle formation. IgE formulation was resistant to aggregation in response to freeze-thaw stress, retaining high monomeric purity. Exposure to thermal stress at elevated temperatures resulted in loss of monomeric purity and aggregation. Agitation stress induced submicron and subvisible aggregation, but monomeric purity was not significantly impacted. MOv18 IgE retains monomeric purity in response to formulation and stress conditions, confirming stability, and crucial for guiding future IgE-based drug development.

ORCID iDs

Considine, Paul, Punnabhum, Panida ORCID logoORCID: https://orcid.org/0009-0002-6830-1072, Davidson, Callum G. ORCID logoORCID: https://orcid.org/0009-0003-8736-9918, Armstrong, Georgina B. ORCID logoORCID: https://orcid.org/0009-0007-3846-0554, Kreiner, Michaela ORCID logoORCID: https://orcid.org/0000-0003-4824-0153, Bax, Heather J., Chauhan, Jitesh, Spicer, James, Josephs, Debra H., Karagiannis, Sophia N., Halbert, Gavin and Rattray, Zahra ORCID logoORCID: https://orcid.org/0000-0002-8371-8549;
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