{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T11:03:29Z","timestamp":1789556609633,"version":"build-2803163510"},"reference-count":101,"publisher":"MDPI AG","issue":"18","license":[{"start":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T00:00:00Z","timestamp":1789516800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Messenger RNA vaccines have moved rapidly from the infectious-disease area into oncology. They now represent an attractive therapeutic option for gastrointestinal (GI) cancers. Personalised constructs, designed to elicit tumour-specific T-cell immunity, have shown acceptable safety and clear immunogenicity in early-phase trials of colorectal and pancreatic cancers. These early signals are encouraging, but several obstacles still exist for routine clinical use: tumour heterogeneity, immune evasion, the difficulty of selecting the right target antigens, and the stability of the delivery platform itself. The possibility of a combination with immune checkpoint inhibitors is currently being explored to deepen and prolong responses, although the durability of benefit remains to be established. In this review, we outline the current landscape of mRNA vaccine development for GI malignancies, with particular attention to delivery strategies and multimodal immunotherapy. Finally, we discuss the directions most likely to help move these agents from the laboratory into everyday clinical practice.<\/jats:p>","DOI":"10.3390\/cells15181673","type":"journal-article","created":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T10:09:17Z","timestamp":1789553357000},"page":"1673","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["mRNA Vaccines as Novel Immunotherapeutic Approaches in Gastrointestinal Cancers"],"prefix":"10.3390","volume":"15","author":[{"given":"Michele","family":"Ghidini","sequence":"first","affiliation":[{"name":"Medical Oncology Division, ASST Sette Laghi, 21100 Varese, Italy"},{"name":"Department of Medicine and Technological Innovation (DiMIT), University of Insubria, 21100 Varese, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2741-8840","authenticated-orcid":false,"given":"Federica","family":"Novazzi","sequence":"additional","affiliation":[{"name":"Department of Medicine and Technological Innovation (DiMIT), University of Insubria, 21100 Varese, Italy"},{"name":"Laboratory of Medical Microbiology and Virology, ASST Sette Laghi, 21100 Varese, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8605-4290","authenticated-orcid":false,"given":"Nerina","family":"Denaro","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Fondazione IRCCS Ca\u2019 Granda Ospedale Maggiore Policlinico, 20122 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5489-5733","authenticated-orcid":false,"given":"Angelica","family":"Petrillo","sequence":"additional","affiliation":[{"name":"Medical Oncology Unit, Ospedale del Mare, 80147 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Margherita","family":"Ratti","sequence":"additional","affiliation":[{"name":"Oncology and Hematology Department, Piacenza General Hospital, 29121 Piacenza, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Massimiliano","family":"Salati","sequence":"additional","affiliation":[{"name":"Modena Cancer Centre, University Hospital of Modena, 41124 Modena, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roberta","family":"Malvaso","sequence":"additional","affiliation":[{"name":"Department of Oncology, Universit\u00e0 Politecnica delle Marche, 60121 Ancona, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3716-7010","authenticated-orcid":false,"given":"Lorenza","family":"Di Marco","sequence":"additional","affiliation":[{"name":"Modena Cancer Centre, University Hospital of Modena, 41124 Modena, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4629-7762","authenticated-orcid":false,"given":"Alessandro","family":"Parisi","sequence":"additional","affiliation":[{"name":"Department of Oncology, Universit\u00e0 Politecnica delle Marche, 60121 Ancona, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jens Claus","family":"Hahne","sequence":"additional","affiliation":[{"name":"NIHR Biomedical Research Centre Leicester, University of Leicester, Leicester LE3 9QP, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,9,16]]},"reference":[{"key":"ref_1","first-page":"229","article-title":"Global cancer statistics 2022: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries","volume":"74","author":"Bray","year":"2024","journal-title":"CA Cancer J. 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