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© 2025 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.

Abstract

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–chitosan 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-γ 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.

Details

Title
Anti-Tumor Efficacy of a Mesothelin-Based Nanovaccine in a KPC Orthotopic Mouse Model of Pancreatic Cancer
Author
Ferrari, Daniele P 1   VIAFID ORCID Logo  ; Özmen Çobanoglu 2 ; Sayedipour, Sana 3 ; Luna, Omar 4 ; Ferkel, Sonia A M 1 ; Agorku, David 5 ; Perez, Yomkippur 6   VIAFID ORCID Logo  ; Cruz, Luis J 3 ; Albericio, Fernando 4   VIAFID ORCID Logo  ; Trottein, François 2   VIAFID ORCID Logo  ; Alves, Frauke 7   VIAFID ORCID Logo  ; Markus, Marietta Andrea 1   VIAFID ORCID Logo  ; Ramos-Gomes, Fernanda 1 

 Translational Molecular Imaging, Max-Planck-Institute for Multidisciplinary Sciences, 37075 Göttingen, Germany 
 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 
 Department of Radiology, Leiden University Medical Center, 2333 ZA Leiden, The Netherlands 
 Department of Organic Chemistry, University of Barcelona, 08028 Barcelona, Spain[email protected] (F.A.) 
 Miltenyi Biotec B.V. & Co. KG, 51429 Bergisch Gladbach, Germany 
 Polypure AS, 1364 Fornebu, Norway; [email protected] 
 Translational Molecular Imaging, Max-Planck-Institute for Multidisciplinary Sciences, 37075 Göttingen, Germany; Department of Haematology and Medical Oncology, Translational Molecular Imaging, University Medical Center Göttingen, 37075 Göttingen, Germany; Institute of Diagnostic and Interventional Radiology, Translational Molecular Imaging, University Medical Center Göttingen, 37075 Göttingen, Germany 
First page
314
Publication year
2025
Publication date
2025
Publisher
MDPI AG
e-ISSN
2076393X
Source type
Scholarly Journal
Language of publication
English
ProQuest document ID
3181826657
Copyright
© 2025 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.