{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,21]],"date-time":"2026-07-21T10:51:27Z","timestamp":1784631087647,"version":"3.55.0"},"reference-count":51,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2025,3,14]],"date-time":"2025-03-14T00:00:00Z","timestamp":1741910400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Marie Sk\u0142odowska-Curie","award":["861190\u2013PAVE"],"award-info":[{"award-number":["861190\u2013PAVE"]}]},{"name":"Marie Sk\u0142odowska-Curie","award":["101016457-FAIRCHARM"],"award-info":[{"award-number":["101016457-FAIRCHARM"]}]},{"DOI":"10.13039\/100010669","name":"H2020 LEIT Information and Communication Technologies","doi-asserted-by":"publisher","award":["861190\u2013PAVE"],"award-info":[{"award-number":["861190\u2013PAVE"]}],"id":[{"id":"10.13039\/100010669","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100010669","name":"H2020 LEIT Information and Communication Technologies","doi-asserted-by":"publisher","award":["101016457-FAIRCHARM"],"award-info":[{"award-number":["101016457-FAIRCHARM"]}],"id":[{"id":"10.13039\/100010669","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Vaccines"],"abstract":"<jats:p>Background\/Objectives: Immunotherapy has shown promising results in some cancers, but its efficacy remains limited in pancreatic ductal adenocarcinoma (PDAC). Vaccines in nanoparticle form (nanovaccines) can incorporate immunostimulating components to induce a potent immune response. As mesothelin (MSLN) is a tumor-associated antigen overexpressed in PDAC, we evaluated the effect of MSLN nanovaccine in a syngeneic orthotopic KPC-PDAC mouse model. Methods: An MSLN peptide combining three MSLN epitopes and two adjuvants, poly I:C and R848, was encapsulated in PLGA\u2013chitosan nanoparticles to generate the nanovaccine. Results: The MSLN nanovaccine was successfully taken up by dendritic cells in vitro and was found in inguinal lymph nodes 24 h after subcutaneous injection into C57BL\/6 mice. Nanovaccine re-stimulation of splenocytes from vaccinated mice led to increased levels of interferon-\u03b3 in vitro compared to unstimulated splenocytes. Higher levels of MSLN-specific IgM and IgG antibodies were detected in the serum of vaccinated mice compared to that of control mice. Three vaccination regimens were tested: a prophylactic scheme that included vaccination before tumor induction and two therapeutic schemes involving early and late vaccination after tumor cell inoculation. MSLN nanovaccination inhibited KPC tumor progression and metastasis and induced higher CD8+ T cell infiltration in the tumor that developed in response to prophylactic and early therapeutic schedules but not in response to a later vaccination approach. Although the nanovaccine treatment elicited higher humoral and cellular antigen-specific responses in tumor-bearing mice for both vaccination strategies, the therapeutic vaccination also increased the expression of exhaustion markers in CD8+ T cells. Conclusions: Our results support the relevance of an MSLN-based nanovaccine as a new immunotherapy treatment for PDAC and propose an innovative method of vaccine delivery using NPs.<\/jats:p>","DOI":"10.3390\/vaccines13030314","type":"journal-article","created":{"date-parts":[[2025,3,14]],"date-time":"2025-03-14T04:29:18Z","timestamp":1741926558000},"page":"314","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Anti-Tumor Efficacy of a Mesothelin-Based Nanovaccine in a KPC Orthotopic Mouse Model of Pancreatic Cancer"],"prefix":"10.3390","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7345-309X","authenticated-orcid":false,"given":"Daniele P.","family":"Ferrari","sequence":"first","affiliation":[{"name":"Translational Molecular Imaging, Max-Planck-Institute for Multidisciplinary Sciences, 37075 G\u00f6ttingen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"\u00d6zmen","family":"\u00c7obanoglu","sequence":"additional","affiliation":[{"name":"Univ. Lille, CNRS, INSERM, CHU Lille, Institut Pasteur de Lille, U1019-UMR 9017-CIIL-Center for Infection and Immunity of Lille, F-59000 Lille, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sana","family":"Sayedipour","sequence":"additional","affiliation":[{"name":"Department of Radiology, Leiden University Medical Center, 2333 ZA Leiden, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Omar","family":"Luna","sequence":"additional","affiliation":[{"name":"Department of Organic Chemistry, University of Barcelona, 08028 Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sonia A. M.","family":"Ferkel","sequence":"additional","affiliation":[{"name":"Translational Molecular Imaging, Max-Planck-Institute for Multidisciplinary Sciences, 37075 G\u00f6ttingen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Agorku","sequence":"additional","affiliation":[{"name":"Miltenyi Biotec B.V. & Co. KG, 51429 Bergisch Gladbach, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6760-7323","authenticated-orcid":false,"given":"Yomkippur","family":"Perez","sequence":"additional","affiliation":[{"name":"Polypure AS, 1364 Fornebu, Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luis J.","family":"Cruz","sequence":"additional","affiliation":[{"name":"Department of Radiology, Leiden University Medical Center, 2333 ZA Leiden, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8946-0462","authenticated-orcid":false,"given":"Fernando","family":"Albericio","sequence":"additional","affiliation":[{"name":"Department of Organic Chemistry, University of Barcelona, 08028 Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3373-1814","authenticated-orcid":false,"given":"Fran\u00e7ois","family":"Trottein","sequence":"additional","affiliation":[{"name":"Univ. Lille, CNRS, INSERM, CHU Lille, Institut Pasteur de Lille, U1019-UMR 9017-CIIL-Center for Infection and Immunity of Lille, F-59000 Lille, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6258-5409","authenticated-orcid":false,"given":"Frauke","family":"Alves","sequence":"additional","affiliation":[{"name":"Translational Molecular Imaging, Max-Planck-Institute for Multidisciplinary Sciences, 37075 G\u00f6ttingen, Germany"},{"name":"Department of Haematology and Medical Oncology, Translational Molecular Imaging, University Medical Center G\u00f6ttingen, 37075 G\u00f6ttingen, Germany"},{"name":"Institute of Diagnostic and Interventional Radiology, Translational Molecular Imaging, University Medical Center G\u00f6ttingen, 37075 G\u00f6ttingen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2305-3394","authenticated-orcid":false,"given":"Marietta Andrea","family":"Markus","sequence":"additional","affiliation":[{"name":"Translational Molecular Imaging, Max-Planck-Institute for Multidisciplinary Sciences, 37075 G\u00f6ttingen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fernanda","family":"Ramos-Gomes","sequence":"additional","affiliation":[{"name":"Translational Molecular Imaging, Max-Planck-Institute for Multidisciplinary Sciences, 37075 G\u00f6ttingen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,3,14]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Liot, S., Balas, J., Aubert, A., Prigent, L., Mercier-Gouy, P., Verrier, B., Bertolino, P., Hennino, A., Valcourt, U., and Lambert, E. 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