Mapping MAGE-A4 expression in solid cancers for targeted therapies

Habigt, Christin;Rottey, Sylvie;Spanggaard, Iben;Lopez, Juanita S.;Roller, Andreas;et.al.
(2025) Frontiers in Oncology — Vol. 15 (2025)

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  • Habigt, ChristinRoche Pharma Research and Early Development, Early Development Oncology, Roche Innovation Center Munich, Penzberg, Germany.
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  • Rottey, SylvieDepartment of Medical Oncology, UZ Gent, Ghent, Belgium.
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  • Spanggaard, IbenDepartment of Oncology, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark.
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  • Lopez, Juanita S.Phase I Drug Development Unit, The Institute of Cancer Research and The Royal Marsden Hospital NHS Foundation Trust, London, United Kingdom.
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  • Galot, Rachelorcid-logoUCLouvain
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  • Roller, AndreasRoche Pharma Research and Early Development, Early Development Oncology, Roche Innovation Center Basel, Basel, Switzerland.
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Abstract
Melanoma-associated antigen A4 (MAGE-A4) is a promising target for anticancer therapy. However, limited contemporary data are available on the details of MAGE-A4 protein expression in different cancer types. In this study, the protein expression of MAGE-A4 is comprehensively studied in patients with unresectable and/or metastatic solid cancers to identify indications of the highest unmet medical need for anti-MAGE-A4 therapy. FFPE tumor sections from 200 patients, predominantly HLA-A*02:01 positive (n = 193), were examined using immunohistochemistry (IHC) to detect MAGE-A4 expression. The patient cohort comprised various cancer types to pinpoint differences in the prevalence and intensity of MAGE-A4 positivity. MAGE-A4 expression was observed in 35% (69 patients) of the overall cohort. Certain cancer types exhibited notably higher frequencies of MAGE-A4 positivity. Specifically, adenoid cystic carcinoma demonstrated the highest prevalence at 82%, followed by liposarcoma at 67%. Ovarian serous/high-grade carcinoma showed a 64% positivity rate, identical to that observed in squamous non-small cell lung cancer (NSCLC). Head and neck squamous cell carcinoma (HNSCC) presented a 60% prevalence, while esophageal cancer had a 54% prevalence of MAGE-A4 expression. These data highlight the variability of MAGE-A4 expression across different cancer types and underscore its relevance as a potential target of novel precision medicines. The significant presence of MAGE-A4 in specific cancers suggests potential for stratified therapeutic approaches and warrants further investigation into its role in oncogenesis and treatment response
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Habigt, C., Rottey, S., Spanggaard, I., Lopez, J. S., Garralda, E., Calvo, E., Bechter, O., Desai, J., Galot, R., Gandhi, L., Heil, F., Rieder, N., Dimitrov, I., Quetglas, I. M., Heichinger, C., Keshelava, N., & Roller, A. (2025). Mapping MAGE-A4 expression in solid cancers for targeted therapies. Frontiers in Oncology, 15. https://doi.org/10.3389/fonc.2025.1484182 (Original work published 2025)