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Evolution and trends in non-viral mRNA Cancer vaccines: A scoping review from 2015 to 2025

Fariborz Nowzari1, Farhad Nowzari2, Mehdi Kian3

  • 1Stem Cells Technology Research Center, Shiraz University of Medical Sciences, Shiraz, Iran.

Vaccine
|December 6, 2025
PubMed

Insights

Messenger RNA (mRNA) cancer vaccines are shifting from ex vivo dendritic cell (DC) approaches to in vivo lipid nanoparticle (LNP) systems. This evolution is linked to specific cancer types and combination immunotherapies.

Area of Science:

  • Oncology
  • Immunology
  • Biotechnology

Background:

  • Non-viral messenger RNA (mRNA)-based cancer vaccines represent a rapidly evolving therapeutic modality.
  • Early research focused on ex vivo dendritic cell (DC) vaccines, while recent advancements favor in vivo lipid nanoparticle (LNP) delivery systems.

Purpose of the Study:

  • To review clinical trials investigating non-viral mRNA cancer vaccines from 2015 to 2025.
  • To analyze trends in delivery platforms (ex vivo DC vs. in vivo LNP) and their association with cancer types.
  • To identify shifts in vaccine strategies, particularly the rise of combination immunotherapies.

Main Methods:

  • Systematic literature search of PubMed and ClinicalTrials.gov.
  • Analysis of 72 early-phase clinical trials.
  • Statistical methods including linear regression and Fisher's exact test.

Main Results:

  • Significant shift observed from ex vivo DC vaccines (dominant 2015-2020) to in vivo LNP delivery post-2021 (p=0.0025).
  • Strong association found between ex vivo DC delivery and brain/CNS cancers (p=0.00042).
  • Increasing use of combination immunotherapies, especially with immune checkpoint inhibitors, since 2019.

Conclusions:

  • The field of mRNA cancer vaccines is transitioning towards in vivo LNP delivery systems.
  • Delivery platform choice shows association with specific cancer types, particularly CNS cancers.
  • Future research should focus on optimizing delivery, improving reporting transparency, and standardization.
Keywords:
CancerClinical trialsDendritic cellsImmunotherapyLipid nanoparticlesNon-viral deliveryRNA vaccines

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