Evolution and trends in non-viral mRNA Cancer vaccines: A scoping review from 2015 to 2025
Nowzari F. Nowzari F. Kian M. Zahedi M. Samimi K. Karimzadeh A. Tanideh N. Mussin N.M. Tamadon A.
25 January 2026Elsevier Ltd
Vaccine
2026#71
This scoping review synthesizes clinical trials from 2015 to 2025 investigating non-viral messenger RNA (mRNA)-based cancer vaccines, emphasizing trends in delivery platforms—ex vivo dendritic cell (DC) vaccines versus in vivo lipid-based systems—and their association with cancer types. A systematic search of PubMed and ClinicalTrials.gov identified 72 early-phase trials, revealing a significant shift from DC-based ex vivo approaches (dominant 2015–2020) to lipid nanoparticle (LNP)-based in vivo delivery post-2021 (p = 0.0025), propelled by advancements from COVID-19 vaccines. Statistical analyses, including linear regression and Fishers exact test, demonstrate a strong association between ex vivo delivery and brain/CNS cancers (p = 0.00042) and no significant correlation between DC vaccine administration routes and cancer types (p = 0.25). The surge in combination immunotherapies, particularly with immune checkpoint inhibitors post-2019, underscores the fields move toward multimodal strategies. This article offers a data-driven roadmap of the fields evolution, highlighting gaps in delivery optimization, reporting transparency, and standardization for future research. Companion articles detail ex vivo DC vaccine strategies and in vivo mRNA vaccine advancements.
Cancer , Clinical trials , Dendritic cells , Immunotherapy , Lipid nanoparticles , Non-viral delivery , RNA vaccines
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Stem Cells Technology Research Center, Shiraz University of Medical Sciences, Shiraz, Iran
Senior Full-Stack Engineer, Kaufland e-commerce, Germany
Medicinal Plant Research Center, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran
Department of Comparative Biomedical Sciences, School of Advanced Medical Sciences and Technologies, Shiraz University of Medical Sciences, Shiraz, Iran
Department of Medicinal Chemistry, School of Pharmacy, Shiraz University of Medical Sciences, Shiraz, Iran
Division of Immunotherapy and Immunoprevention, German Cancer Research Center (DKFZ), Heidelberg, Germany
Faculty of Biosciences, Heidelberg University, Heidelberg, Germany
Department of Medical Biotechnology, School of Advanced Medical Sciences and Technologies, Shiraz University of Medical Sciences, Shiraz, Iran
Department of Pharmacology, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran
Department of Surgery No. 2, West Kazakhstan Marat Ospanov Medical University, Aktobe, Kazakhstan
Stem Cells Technology Research Center
Senior Full-Stack Engineer
Medicinal Plant Research Center
Department of Comparative Biomedical Sciences
Department of Medicinal Chemistry
Division of Immunotherapy and Immunoprevention
Faculty of Biosciences
Department of Medical Biotechnology
Department of Pharmacology
Department of Surgery No. 2
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