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  • Review Article
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Cancer mRNA vaccines: clinical advances and future opportunities

Nature Reviews Clinical Oncology (2024)Cite this article

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Abstract

mRNA vaccines have been revolutionary in terms of their rapid development and prevention of SARS-CoV-2 infections during the COVID-19 pandemic, and this technology has considerable potential for application to the treatment of cancer. Compared with traditional cancer vaccines based on proteins or peptides, mRNA vaccines reconcile the needs for both personalization and commercialization in a manner that is unique to each patient but not beholden to their HLA haplotype. A further advantage of mRNA vaccines is the availability of engineering strategies to improve their stability while retaining immunogenicity, enabling the induction of complementary innate and adaptive immune responses. Thus far, no mRNA-based cancer vaccines have received regulatory approval, although several phase I–II trials have yielded promising results, including in historically poorly immunogenic tumours. Furthermore, many early phase trials testing a wide range of vaccine designs are currently ongoing. In this Review, we describe the advantages of cancer mRNA vaccines and advances in clinical trials using both cell-based and nanoparticle-based delivery methods, with discussions of future combinations and iterations that might optimize the activity of these agents.

Key points

  • The advent of mRNA-based vaccines against SARS-CoV-2 has ushered in a new era of mRNA vaccines against other infectious diseases as well as cancer.

  • Advantages of directly injected mRNA vaccines include safety and flexibility in terms of the speed with which personalized epitopes or antigens can be produced in the form of mRNA.

  • mRNA is a labile molecule and is best delivered in nanoparticles, which are not currently developed to target specific cell types for the induction of immune responses. Alternatively, mRNA can be loaded into antigen-presenting cells that can then be administered as a vaccine.

  • SARS-CoV-2 vaccines use mRNA incorporating modified nucleotides to minimize the risk of a type I interferon response. However, this response might be beneficial in the setting of cancer vaccines, which must generate immune responses against antigens that are overexpressed self-antigens or those that result in only slightly altered proteins and are therefore likely to be less immunogenic.

  • The future of mRNA vaccines will include optimization of the nanoparticles used to deliver the vaccine as well as of the mRNA itself.

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Fig. 1: Challenges to the success of cancer vaccines.
Fig. 2: mRNA-loaded DC trafficking in the presence of a recall antigen.
Fig. 3: RNA-loaded DC manufacturing.
Fig. 4: Different types of RNA-loaded nanoparticles in clinical trials.
Fig. 5: mRNA backbone design.

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Authors and Affiliations

  1. Preston A. Wells Jr. Center for Brain Tumour Therapy, University of Florida, Gainesville, FL, USA

    Elias J. Sayour & Duane A. Mitchell

  2. Lillian S. Wells Department of Neurosurgery, University of Florida, Gainesville, FL, USA

    Elias J. Sayour & Duane A. Mitchell

  3. Department of Surgery, Duke University School of Medicine, Durham, NC, USA

    David Boczkowski & Smita K. Nair

  4. Department of Neurosurgery, Duke University School of Medicine, Durham, NC, USA

    Smita K. Nair

  5. Department of Pathology, Duke University School of Medicine, Durham, NC, USA

    Smita K. Nair

  6. Duke Cancer Institute, Duke University School of Medicine, Durham, NC, USA

    Smita K. Nair

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E.J.S., D.B. and S.K.N. researched data for the manuscript. E.J.S. and D.B. wrote the manuscript. All authors made a substantial contribution to discussions of content and reviewed and/or edited the manuscript prior to submission.

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Correspondence to Smita K. Nair.

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Competing interests

E.J.S. has acted as a consultant of Siren Biotechnology and is listed on pending patent applications relating to technologies discussed in this manuscript that are optioned to license to iOncologi, Inc. D.A.M. is listed on pending patent applications on technologies discussed in this manuscript that are optioned to license to iOncologi, Inc. and holds ownership interests in iOncologi, Inc. S.K.N. and D.B. declare no competing interests.

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Sayour, E.J., Boczkowski, D., Mitchell, D.A. et al. Cancer mRNA vaccines: clinical advances and future opportunities. Nat Rev Clin Oncol (2024). https://doi.org/10.1038/s41571-024-00902-1

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