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Neoantigen-specific mRNA/DC vaccines for effective anticancer immunotherapy

Genes & Immunity volume 25, pages 514–524 (2024)Cite this article

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Abstract

The development of personalized anticancer vaccines based on neoantigens represents a new direction in cancer immunotherapy. The latest advancement in dendritic cell (DC) tumor vaccine construction involves loading DC with mRNA-encoding neoantigens, which allows for rapid production and is suitable for personalized preparation. Cell-penetrating peptides (CPPs) are emerging as biological delivery systems in which negatively charged nucleic acids can be wound onto the cationic CPP backbone to form nanoscale complexes. This preparation method facilitates standardization. If DC can express and present neoantigen mRNA at high levels, it holds promising application potential. In this study, we developed a neoantigen-mRNA/DC vaccine using candidate neoantigens from mouse colon cancer (MC38) and examined its immune and antitumor effects. The results demonstrated that neoantigen-mRNA/DC vaccines induced strong T cell immune responses and exhibited significant antitumor effects, effectively preventing tumor growth. Our study provides an experimental basis for further optimizing the preparation of DC vaccines and reducing their costs.

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Fig. 1: Schematic representation of the design for neoantigen mRNA vaccine.
Fig. 2: Characterization of mRNA-RALA complexes.
Fig. 3: RALA-based formulations allow efficient mRNA uptake and protein expression in dendritic cells.
Fig. 4: The neoantigen-mRNA/DC vaccine enhances the function of tumor infiltrating lymphocytes.
Fig. 5: Delivery and immune enhancement efficacy of neoantigen-mRNA/DC vaccine.
Fig. 6: Anti-tumor effects of neoantigen-mRNA/DC vaccine in vivo.
Fig. 7: Anti-tumor effects of non-neoantigen mRNA/DC vaccine in vivo.

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Data availability

The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request.

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Acknowledgements

We would like to thank the Air Force Medical University for the supply of germ-free mice and MC38 cell line.

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Authors and Affiliations

  1. Translational Medicine Center of Shaanxi Provincial People’s Hospital, Xi’an, 710068, China

    Wenli Zhang, Guo Chen & Zifan Lu

  2. Medical Laboratory Center of Shaanxi Provincial People’s Hospital, Xi’an, 710068, China

    Jiahao Guan

  3. Department of Military Preventive Medicine, Air Force Medical University, Xi’an, 710032, China

    Wenwen Wang

  4. Traditional Chinese Medicine of Shouguang Hospital, Shouguang, 262700, China

    Li Fan

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Contributions

Wenli Zhang: data curation; formal analysis; investigation; supervision; validation; visualization; writing—original draft. Jiahao Guan: methodology; project administration; software; visualization. Wenwen Wang: investigation; methodology; supervision. Guo Chen: supervision; validation. Li Fan: supervision; writing—review and editing; Zifan Lu: supervision; writing—review and editing; project administration.

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Correspondence to Zifan Lu.

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All methods were performed in accordance with the relevant guidelines and regulations. All the animal experiments were approved by the Institutional Animal Experiment Administration Committee of the Fourth Military Medical University (Number: 20241257).

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Zhang, W., Guan, J., Wang, W. et al. Neoantigen-specific mRNA/DC vaccines for effective anticancer immunotherapy. Genes Immun 25, 514–524 (2024). https://doi.org/10.1038/s41435-024-00305-3

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