{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T14:47:53Z","timestamp":1790952473389,"version":"4.1.0"},"reference-count":45,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2026,2,22]],"date-time":"2026-02-22T00:00:00Z","timestamp":1771718400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100011789","name":"Science & Technology Development Plan of Jilin Province","doi-asserted-by":"publisher","award":["20240402044GH"],"award-info":[{"award-number":["20240402044GH"]}],"id":[{"id":"10.13039\/501100011789","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Scientific Research Project of Education Department of Jilin Province","award":["JJKH20261420KJ"],"award-info":[{"award-number":["JJKH20261420KJ"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>DNA-based cancer vaccines represent a safe and promising immunotherapeutic strategy, but their clinical efficacy is often limited by weak immunogenicity, primarily due to inefficient antigen cross-presentation. To overcome this challenge, the MHC class I trafficking domain (MITD) can be fused to tumor antigens to enhance their intracellular routing in dendritic cells (DCs), thereby promoting the efficiency of cross-presentation. In addition, incorporation of CD4+ T cell epitopes, such as PADRE or P2P16, can robustly activate CD4+ T cells, further amplifying antitumor immunity. Thus, combining MITD with CD4+ epitopes is expected to synergistically improve DNA vaccine potency. Mesothelin (MSLN), a tumor-associated antigen highly expressed in pancreatic cancer, was selected as the target in this study. We designed MSLN-targeted DNA vaccines incorporating MITD together with either PADRE or P2P16. In a Panc02 murine model, the MITD\u2013PADRE construct, a novel design, elicited stronger immune responses and more effective antitumor activity compared to other formulations. To further counteract immunosuppression, we combined the vaccine with gemcitabine, which enhanced therapeutic efficacy. Together, these findings demonstrate that integrating PADRE with MITD in MSLN-targeted DNA vaccines offers a promising combinatorial strategy for advancing pancreatic cancer immunotherapy.<\/jats:p>","DOI":"10.3390\/ijms27042039","type":"journal-article","created":{"date-parts":[[2026,2,23]],"date-time":"2026-02-23T08:58:21Z","timestamp":1771837101000},"page":"2039","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["A DNA Vaccine Incorporating the MHC Class I Trafficking Domain and PADRE Epitope Enhances Antitumor Immunity in a Murine Pancreatic Cancer Model"],"prefix":"10.3390","volume":"27","author":[{"given":"Simiao","family":"Cao","sequence":"first","affiliation":[{"name":"National Engineering Laboratory for AIDS Vaccine, School of Life Science, Jilin University, Changchun 130012, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-8758-6316","authenticated-orcid":false,"given":"Guoxuan","family":"Bai","sequence":"additional","affiliation":[{"name":"National Engineering Laboratory for AIDS Vaccine, School of Life Science, Jilin University, Changchun 130012, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qimuge","family":"Wuri","sequence":"additional","affiliation":[{"name":"National Engineering Laboratory for AIDS Vaccine, School of Life Science, Jilin University, Changchun 130012, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiayin","family":"Li","sequence":"additional","affiliation":[{"name":"National Engineering Laboratory for AIDS Vaccine, School of Life Science, Jilin University, Changchun 130012, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaojing","family":"Zhang","sequence":"additional","affiliation":[{"name":"National Engineering Laboratory for AIDS Vaccine, School of Life Science, Jilin University, Changchun 130012, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhilin","family":"Han","sequence":"additional","affiliation":[{"name":"National Engineering Laboratory for AIDS Vaccine, School of Life Science, Jilin University, Changchun 130012, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hui","family":"Wu","sequence":"additional","affiliation":[{"name":"National Engineering Laboratory for AIDS Vaccine, School of Life Science, Jilin University, Changchun 130012, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiaxin","family":"Wu","sequence":"additional","affiliation":[{"name":"National Engineering Laboratory for AIDS Vaccine, School of Life Science, Jilin University, Changchun 130012, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-9202-677X","authenticated-orcid":false,"given":"Chu","family":"Wang","sequence":"additional","affiliation":[{"name":"National Engineering Laboratory for AIDS Vaccine, School of Life Science, Jilin University, Changchun 130012, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7739-1386","authenticated-orcid":false,"given":"Xianghui","family":"Yu","sequence":"additional","affiliation":[{"name":"National Engineering Laboratory for AIDS Vaccine, School of Life Science, Jilin University, Changchun 130012, China"},{"name":"Key Laboratory for Molecular Enzymology and Engineering, The Ministry of Education, School of Life Sciences, Jilin University, Changchun 130012, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3074-1817","authenticated-orcid":false,"given":"Haihong","family":"Zhang","sequence":"additional","affiliation":[{"name":"National Engineering Laboratory for AIDS Vaccine, School of Life Science, Jilin University, Changchun 130012, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,2,22]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"144","DOI":"10.1038\/s41586-023-06063-y","article-title":"Personalized RNA neoantigen vaccines stimulate T cells in pancreatic cancer","volume":"618","author":"Rojas","year":"2023","journal-title":"Nature"},{"key":"ref_2","first-page":"209","article-title":"Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries","volume":"71","author":"Sung","year":"2021","journal-title":"Ca-A Cancer J. 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