mRNA therapeutics in cancer immunotherapy

Synthetic mRNA provides a template for the synthesis of any given protein, protein fragment or peptide and lends itself to a broad range of pharmaceutical applications, including different modalities of cancer immunotherapy. With the ease of rapid, large scale Good Manufacturing Practice-grade mRNA...

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Bibliographic Details
Published in:	Molecular cancer Vol. 20; no. 1; pp. 69 - 24
Main Authors:	Beck, Jan D., Reidenbach, Daniel, Salomon, Nadja, Sahin, Ugur, Türeci, Özlem, Vormehr, Mathias, Kranz, Lena M.
Format:	Journal Article
Language:	English
Published:	London BioMed Central 15.04.2021 BioMed Central Ltd Springer Nature B.V BMC
Subjects:	2021 mRNA Special Issue Adjuvanticity Animals Antibodies Antibodies - genetics Antibodies - immunology Antigen Presentation - immunology Antigen-Presenting Cells - immunology Antigen-Presenting Cells - metabolism Antigens, Neoplasm - genetics Antigens, Neoplasm - immunology Antiviral agents Antiviral drugs Basiliximab Biomarkers, Tumor Biomedical and Life Sciences Biomedicine Cancer Cancer immunotherapy Cancer Research Cancer vaccines Cancer Vaccines - administration & dosage Cancer Vaccines - genetics Cancer Vaccines - immunology Care and treatment Chimeric antigen receptors Cytokines - metabolism Dendritic Cells - immunology Dendritic Cells - metabolism Double-stranded RNA Drug therapy Genetic Therapy - methods Health aspects Humans Immune response Immunization Immunologic Factors - genetics Immunomodulation Immunomodulators Immunomodulatory proteins Immunoreceptors Immunotherapy Immunotherapy - methods Innate immunity Kinases Lymphatic system Lymphocytes T Messenger RNA mRNA Nanoparticles Neoantigens Neoplasms - etiology Neoplasms - pathology Neoplasms - therapy Nucleosides Oncology Pattern recognition receptors Pharmacodynamics Pharmacokinetics Prostate cancer Protein biosynthesis Receptors, Antigen, T-Cell - genetics Receptors, Antigen, T-Cell - immunology Recombinant proteins Review RNA, Messenger - administration & dosage RNA, Messenger - chemistry RNA, Messenger - genetics RNA, Messenger - immunology T cells T-Lymphocytes - immunology T-Lymphocytes - metabolism Tetanus antitoxin Transfection Tumor antigens Vaccination Vaccines Viral antibodies Cancer vaccines Immunoreceptors CARs Messenger RNA Antibodies Cancer immunotherapy Immunomodulatory proteins
ISSN:	1476-4598, 1476-4598
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Summary:	Synthetic mRNA provides a template for the synthesis of any given protein, protein fragment or peptide and lends itself to a broad range of pharmaceutical applications, including different modalities of cancer immunotherapy. With the ease of rapid, large scale Good Manufacturing Practice-grade mRNA production, mRNA is ideally poised not only for off-the shelf cancer vaccines but also for personalized neoantigen vaccination. The ability to stimulate pattern recognition receptors and thus an anti-viral type of innate immune response equips mRNA-based vaccines with inherent adjuvanticity. Nucleoside modification and elimination of double-stranded RNA can reduce the immunomodulatory activity of mRNA and increase and prolong protein production. In combination with nanoparticle-based formulations that increase transfection efficiency and facilitate lymphatic system targeting, nucleoside-modified mRNA enables efficient delivery of cytokines, costimulatory receptors, or therapeutic antibodies. Steady but transient production of the encoded bioactive molecule from the mRNA template can improve the pharmacokinetic, pharmacodynamic and safety properties as compared to the respective recombinant proteins. This may be harnessed for applications that benefit from a higher level of expression control, such as chimeric antigen receptor (CAR)-modified adoptive T-cell therapies. This review highlights the advancements in the field of mRNA-based cancer therapeutics, providing insights into key preclinical developments and the evolving clinical landscape.
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ISSN:	1476-4598 1476-4598
DOI:	10.1186/s12943-021-01348-0