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Review
. 2020 Dec 18;8(4):776.
doi: 10.3390/vaccines8040776.

Neo-Antigen mRNA Vaccines

Arthur Esprit  1 , Wout de Mey  1 , Rajendra Bahadur Shahi  1 , Kris Thielemans  1 , Lorenzo Franceschini  1 , Karine Breckpot  1
Affiliations
Review

Neo-Antigen mRNA Vaccines

Arthur Esprit et al. Vaccines (Basel). .

Abstract

The interest in therapeutic cancer vaccines has caught enormous attention in recent years due to several breakthroughs in cancer research, among which the finding that successful checkpoint blockade treatments reinvigorate neo-antigen-specific T cells and that successful adoptive cell therapies are directed towards neo-antigens. Neo-antigens are cancer-specific antigens, which develop from somatic mutations in the cancer cell genome that can be highly immunogenic and are not subjected to central tolerance. As the majority of neo-antigens are unique to each patient's cancer, a vaccine technology that is flexible and potent is required to develop personalized neo-antigen vaccines. In vitro transcribed mRNA is such a technology platform and has been evaluated for delivery of neo-antigens to professional antigen-presenting cells both ex vivo and in vivo. In addition, strategies that support the activity of T cells in the tumor microenvironment have been developed. These represent a unique opportunity to ensure durable T cell activity upon vaccination. Here, we comprehensively review recent progress in mRNA-based neo-antigen vaccines, summarizing critical milestones that made it possible to bring the promise of therapeutic cancer vaccines within reach.

Keywords: T cell; cancer; dendritic cell; mRNA; neo-antigen; vaccine.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Key components of in vitro transcribed mRNA that determine the level and duration of expression of the encoded protein. The components that can be modulated are shown in blue, while the effect of modulating these components is shown in green. Abbreviations: 3′ poly-A, three prime polyadenylic acid tail; 5′ cap, five prime cap; PRR, pattern recognition receptor; UTR, untranslated region.
Figure 2
Figure 2
Schematic representation of the workflow for neo-antigen identification. Abbreviations: IP, immunoprecipitation; MAE, mild acid elution; MS, mass spectrometry; NGS, next-generation sequencing; WGS, whole exome sequencing; WES: whole exome sequencing.
Figure 3
Figure 3
Timeline showing discoveries and advances in the development of mRNA-based cancer vaccines. Abbreviations: 3′ poly-A, three prime polyadenylic acid tail; 5′ cap, five prime cap; mRNA, messenger RNA; LNP, lipid nanoparticles; DCs, dendritic cells.
See this image and copyright information in PMC

References

    1. Benteyn D., Heirman C., Bonehill A., Thielemans K., Breckpot K. mRNA-based dendritic cell vaccines. Expert Rev. Vaccines. 2015;14:161–176. doi: 10.1586/14760584.2014.957684. - DOI - PubMed
    1. Bonehill A., Heirman C., Tuyaerts S., Michiels A., Breckpot K., Brasseur F., Zhang Y., Van Der Bruggen P., Thielemans K. Messenger RNA-electroporated dendritic cells presenting MAGE-A3 simultaneously in HLA class I and class II molecules. J. Immunol. 2004;172:6649–6657. doi: 10.4049/jimmunol.172.11.6649. - DOI - PubMed
    1. Verbeke R., Lentacker I., Breckpot K., Janssens J., Van Calenbergh S., De Smedt S.C., Dewitte H. Broadening the Message: A Nanovaccine Co-loaded with Messenger RNA and α-GalCer Induces Antitumor Immunity through Conventional and Natural Killer T Cells. ACS Nano. 2019;13:1655–1669. doi: 10.1021/acsnano.8b07660. - DOI - PubMed
    1. Hunder N.N., Wallen H., Cao J., Hendricks D.W., Reilly J.Z., Rodmyre R., Jungbluth A., Gnjatic S., Thompson J.A., Yee C. Treatment of metastatic melanoma with autologous CD4+ T cells against NY-ESO-1. N. Engl. J. Med. 2008;358:2698–2703. doi: 10.1056/NEJMoa0800251. - DOI - PMC - PubMed
    1. Quezada S.A., Simpson T.R., Peggs K.S., Merghoub T., Vider J., Fan X., Blasberg R., Yagita H., Muranski P., Antony P.A., et al. Tumor-reactive CD4(+) T cells develop cytotoxic activity and eradicate large established melanoma after transfer into lymphopenic hosts. J. Exp. Med. 2010;207:637–650. doi: 10.1084/jem.20091918. - DOI - PMC - PubMed