{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,4]],"date-time":"2026-08-04T18:44:16Z","timestamp":1785869056745,"version":"3.56.0"},"reference-count":158,"publisher":"MDPI AG","issue":"19","license":[{"start":{"date-parts":[[2025,10,2]],"date-time":"2025-10-02T00:00:00Z","timestamp":1759363200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"\u201dIuliu Ha\u021bieganu\u201d University of Medicine and Pharmacy Cluj-Napoca","award":["32\/52\/4\/16.12.2024"],"award-info":[{"award-number":["32\/52\/4\/16.12.2024"]}]}],"content-domain":{"domain":["www.mdpi.com"],"crossmark-restriction":true},"short-container-title":["IJMS"],"abstract":"<jats:p>Pancreatic ductal adenocarcinoma (PDAC) remains one of the deadliest malignancies, marked by late diagnosis, limited responsiveness to conventional therapies, and an immunosuppressive tumor microenvironment. While immunotherapy has transformed treatment paradigms in several cancers, its efficacy in PDAC has been minimal. Oncolytic viruses and therapeutic cancer vaccines have emerged as promising immunotherapeutic strategies designed to stimulate robust, tumor-specific immune responses and reshape the immune landscape. However, despite encouraging preclinical data, clinical translation in PDAC has been largely disappointing. This review critically evaluates the design, delivery, and efficacy of oncolytic virotherapy and cancer vaccines in PDAC, examining barriers such as stromal desmoplasia, immune exclusion, and tumor heterogeneity. We also explore combination strategies integrating checkpoint inhibitors, chemotherapy, radiotherapy, and stromal modulation to overcome resistance. Ultimately, the viability of these approaches hinges on a clearer understanding of their mechanistic limitations and the refinement of delivery platforms. These factors will determine whether oncolytic viruses and cancer vaccines can be successfully repositioned within the therapeutic arsenal or warrant reevaluation in the evolving landscape of PDAC treatment.<\/jats:p>","DOI":"10.3390\/ijms26199640","type":"journal-article","created":{"date-parts":[[2025,10,2]],"date-time":"2025-10-02T16:18:33Z","timestamp":1759421913000},"page":"9640","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Design and Efficacy of Oncolytic Viruses and Antitumor Vaccines: A Dead End in the Immunotherapy of Pancreatic Cancer?"],"prefix":"10.3390","volume":"26","author":[{"given":"Eduard","family":"Achim","sequence":"first","affiliation":[{"name":"Analytical Chemistry Department, Faculty of Pharmacy, \u201cIuliu Ha\u0163ieganu\u201d University of Medicine and Pharmacy, 4 Louis Pasteur St., 400349 Cluj-Napoca, Romania"},{"name":"Faculty of Medicine, \u201cIuliu Ha\u021bieganu\u201d University of Medicine and Pharmacy, 400012 Cluj-Napoca, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-4144-7532","authenticated-orcid":false,"given":"Elena","family":"P\u00eerlici","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, \u201cIuliu Ha\u021bieganu\u201d University of Medicine and Pharmacy, 400012 Cluj-Napoca, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4158-3324","authenticated-orcid":false,"given":"Cecilia","family":"Cristea","sequence":"additional","affiliation":[{"name":"Analytical Chemistry Department, Faculty of Pharmacy, \u201cIuliu Ha\u0163ieganu\u201d University of Medicine and Pharmacy, 4 Louis Pasteur St., 400349 Cluj-Napoca, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2572-6724","authenticated-orcid":false,"given":"Mihaela","family":"Tertis","sequence":"additional","affiliation":[{"name":"Analytical Chemistry Department, Faculty of Pharmacy, \u201cIuliu Ha\u0163ieganu\u201d University of Medicine and Pharmacy, 4 Louis Pasteur St., 400349 Cluj-Napoca, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,10,2]]},"reference":[{"key":"ref_1","first-page":"7","article-title":"Cancer Statistics, 2021","volume":"71","author":"Siegel","year":"2021","journal-title":"CA Cancer J. 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