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Here, we present an approach and key considerations for developing a safe ex vivo mRNA-based vaccine potentially targeting EC.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Based on expression analysis in patient-derived endometrial tumor tissues, we identify two potential targets \u2013 fibroblast activation protein (FAP) and melanoma-associated antigen A4 (MAGEA4) \u2013 for immunotherapy using an ex vivo vaccine setting. We optimized the individual components of the mRNA expression cassette to enhance translation fidelity and antigen expression.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>We selected an optimal 5\u2032 untranslated region (UTR) and fine-tuned the translation termination signal to prevent readthrough and generation of unintended neoantigens. Functionally, the ex vivo mRNA vaccine elicited a robust T cell response, particularly when combining both FAP and MAGEA4 antigens. MAGEA4 expression correlated with disease severity in EC tumor tissue, reinforcing its relevance as both a prognostic marker and immunotherapeutic target. Its combination with FAP, expressed by both EC cells and cancer-associated fibroblasts, as part of the tumor microenvironment, may facilitate immune evasion and promote tumor infiltration.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Our data provides evidence that FAP and MAGEA4 antigens delivered via mRNA can drive effective T cell activation. This proof-of-concept study establishes a framework for developing immune-based interventions and more effective treatment strategies for patients with EC.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1186\/s12967-025-07497-w","type":"journal-article","created":{"date-parts":[[2025,12,5]],"date-time":"2025-12-05T03:05:03Z","timestamp":1764903903000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["mRNA-based immunotherapy platform targeting endometrial cancer"],"prefix":"10.1186","volume":"24","author":[{"given":"Moritz","family":"Freyberg","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martha","family":"Dierks","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Norbert","family":"Nass","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher","family":"George","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria","family":"Geffken","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Atanas","family":"Ignatov","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas","family":"Kalinski","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9478-8825","authenticated-orcid":false,"given":"Zoya","family":"Ignatova","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,12,5]]},"reference":[{"key":"7497_CR1","doi-asserted-by":"publisher","first-page":"88","DOI":"10.1038\/s41572-021-00324-8","volume":"7","author":"V Makker","year":"2021","unstructured":"Makker V, MacKay H, Ray-Coquard I, Levine DA, Westin SN, Aoki D, Oaknin A. 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