Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2022 Oct;23(10):e450-e458.
doi: 10.1016/S1470-2045(22)00372-2.

Clinical advances and ongoing trials on mRNA vaccines for cancer treatment

Cathrine Lund Lorentzen  1 , John B Haanen  2 , Özcan Met  1 , Inge Marie Svane  3
Affiliations
Review

Clinical advances and ongoing trials on mRNA vaccines for cancer treatment

Cathrine Lund Lorentzen et al. Lancet Oncol. 2022 Oct.

Erratum in

  • Correction to Lancet Oncol 2022; 23: e450-58.
    [No authors listed] [No authors listed] Lancet Oncol. 2022 Nov;23(11):e492. doi: 10.1016/S1470-2045(22)00608-8. Epub 2022 Oct 7. Lancet Oncol. 2022. PMID: 36216019 Free PMC article. No abstract available.

Abstract

Years of research exploring mRNA vaccines for cancer treatment in preclinical and clinical trials have set the stage for the rapid development of mRNA vaccines during the COVID-19 pandemic. Therapeutic cancer vaccines based on mRNA are well tolerated, and the inherent advantage in ease of production, which rivals the best available conventional vaccine manufacture methods, renders mRNA vaccines a promising option for cancer immunotherapy. Technological advances have optimised mRNA-based vaccine stability, structure, and delivery methods, and multiple clinical trials investigating mRNA vaccine therapy are now enrolling patients with various cancer diagnoses. Although therapeutic mRNA-based cancer vaccines have not yet been approved for standard treatment, encouraging results from early clinical trials with mRNA vaccines as monotherapy and in combination with checkpoint inhibitors have been obtained. This Review summarises the latest clinical advances in mRNA-based vaccines for cancer treatment and reflects on future perspectives and challenges for this new and promising treatment approach.

PubMed Disclaimer

Conflict of interest statement

Declaration of interests IMS reports having lectured for or having had advisory board relationships with Bristol Myers Squibb, MSD, Sanofi Aventis, Pierre Fabre, IO Biotech, Novartis, TILT Biotherapeutics, and Novo Nordisk; research grants from Bristol Myers Squibb, Adaptimmune, Lytix biopharma, IO Biotech, and TILT Biotherapeutics; and is a co-founder and shareholder for IO Biotech, a company that is developing peptide vaccines targeting immune regulation. IO Biotech is a spin-out of Copenhagen University Hospital and has no approved products at the time of writing; an IDO and PD-L1 targeting peptide vaccine for melanoma has been granted Breakthrough Therapy designation by the FDA and is being tested in a phase 3 trial (NCT05155254). The same vaccine is also in phase 2 trials (NCT05077709 and NCT05280314) in other cancer types (including bladder cancer and head and neck cancer). An additional peptide vaccine targeting arginase is being tested in solid cancers in a phase 1 trial. IO Biotech has no interests in RNA vaccines. JBH reports research grants from Amgen, Asher Bio, BioNTech, Bristol Myers Squibb, MSD, and Novartis; had advisory board relationships with Achilles Therapeutics, BioNTech, Bristol Myers Squibb, Ipsen, Iovance Bio, Instil Bio, MSD, Merck Serono, Neogene Therapeutics, Novartis, Pfizer, PokeAcel, Roche, Sanofi, and T-Knife; and holds stock options in Neogene Therapeutics, a company that is developing T-cell receptor gene modified T cells targeting neoantigens. The first neoantigen-specific TCR gene therapy for the treatment of solid cancers is planned for testing in a phase 1 clinical trial. Neogene Therapeutics has no interests in RNA vaccines. CLL and ÖM declare no competing interests.

Figures

Figure
Figure
mRNA-based vaccine mode of action mRNA is taken up by antigen-presenting cells and peptides are loaded on MHC class I for antigen-specific CD8+ T-cell activation. Extracellular proteins are cross-presented on MHC class I or loaded on MHC class II for CD4+ T-cell activation. CD4+ T cells can co-activate protein-specific B cells, and B cells can activate CD4+ T cells after B-cell receptor-mediated antigen internalisation.
See this image and copyright information in PMC

References

    1. Dolgin E. The tangled history of mRNA vaccines. Nature. 2021;597:318–324. - PubMed
    1. Karikó K, Muramatsu H, Welsh FA, et al. Incorporation of pseudouridine into mRNA yields superior nonimmunogenic vector with increased translational capacity and biological stability. Mol Ther. 2008;16:1833–1840. - PMC - PubMed
    1. Guan S, Rosenecker J. Nanotechnologies in delivery of mRNA therapeutics using nonviral vector-based delivery systems. Gene Ther. 2017;24:133–143. - PubMed
    1. Thess A, Grund S, Mui BL, et al. Sequence-engineered mRNA without chemical nucleoside modifications enables an effective protein therapy in large animals. Mol Ther. 2015;23:1456–1464. - PMC - PubMed
    1. Kowalzik F, Schreiner D, Jensen C, Teschner D, Gehring S, Zepp F. mRNA-based vaccines. Vaccines. 2021;9:390. - PMC - PubMed