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An RNA toolbox for cancer immunotherapy
Abstract
Cancer immunotherapy has revolutionized oncology practice. However, current protein and cell therapy tools used in cancer immunotherapy are far from perfect, and there is room for improvement regarding their efficacy and safety. RNA-based structures have diverse functions, ranging from gene expression and gene regulation to pro-inflammatory effects and the ability to specifically bind different molecules. These functions make them versatile tools that may advance cancer vaccines and immunomodulation, surpassing existing approaches. These technologies should not be considered as competitors of current immunotherapies but as partners in synergistic combinations and as a clear opportunity to reach more efficient and personalized results. RNA and RNA derivatives can be exploited therapeutically as a platform to encode protein sequences, provide innate pro-inflammatory signals to the immune system (such as those denoting viral infection), control the expression of other RNAs (including key immunosuppressive factors) post-transcriptionally and conform structural scaffoldings binding proteins that control immune cells by modifying their function. Nascent RNA immunotherapeutics include RNA vaccines encoding cancer neoantigens, mRNAs encoding immunomodulatory factors, viral RNA analogues, interference RNAs and protein-binding RNA aptamers. These approaches are already in early clinical development with promising safety and efficacy results.
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“RNA vaccines, for example, have exhibited encouraging results in both infection therapy and cancer immunotherapy.[6, 7, 11–15]”
From RNA delivery biomaterials for the treatment of genetic and rare diseases (2019) · cites this paper as [7]
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RNA Aptamers Targeting Integrin α5β1 as Probes for Cyto- and Histofluorescence in Glioblastoma
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Lipid nanomaterials-based RNA therapy and cancer treatment
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An OX40L mRNA vaccine inhibits the growth of hepatocellular carcinoma
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“The Kozak sequence was added to the 5′ end (17, 18).”
MethodCurrent advances in cancer vaccines targeting NY-ESO-1 for solid cancer treatment
Zhou, H., Ma, Y., Liu, F., Li, B., Qiao, D., Ren, P., & Wang, M. (2023) · Frontiers in Immunology · doi:10.3389/fimmu.2023.1255799 · Cited by 46
“…and cellular responses; fi nally, mRNA vaccines can be produced quickly at low cost (36). mRNA cancer vaccines can be custom-designed to target speci fi c tumor antigens expressed by cancer cells, stimulating robust in vivo immune responses mediated by T cells or B cells against the tumors (37, 38).”
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“Plasmid DN A w as initially pursued as a ther a peutic v ector [ 7 ], ho w e v er, IVT of mRNA had v arious adv anta ges in ther a peu-tic applications, including low toxicity and high translatability in both dividing and non-dividing cells, as RNA only needs to be internalized into the cytoplasm (…”
BackgroundBreakthrough concepts in immune-oncology: Cancer vaccines at the bedside
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Promising RNA-based cancer gene therapy using extracellular vesicles for drug delivery
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Nanoformulations targeting immune cells for cancer therapy: mRNA therapeutics
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Cytidine Acetylation Yields a Noninflammatory Synthetic Messenger RNA
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High-Throughput Automation of Endosomolytic Polymers for mRNA Delivery
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Boosting Antitumor Response by Costimulatory Strategies Driven to 4-1BB and OX40 T-cell Receptors
Mascarelli, D. E., Rosa, R. S. M., Toscaro, J. M., Semionatto, I. F., Ruas, L. P., Fogagnolo, C. T., Lima, G. C., & Bajgelman, M. C. (2021) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2021.692982 · Cited by 33
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“5 Besides treatments with epigenetic drugs (including hypomethylating agents) or splicing modulators, a promising approach to enhance expression of tumor neoantigens by inhibiting the nonsense-mediated RNA decay (NMD) pathway in cancer cells.”
CircRNAs: functions and emerging roles in cancer and immunotherapy
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Bioinspired Spatiotemporal Management toward RNA Therapies
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Recent Developments in Aptamer-Based Sensors for Diagnostics
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Aptamers as Theragnostic Tools in Prostate Cancer
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Metadata
- Authors
- Pastor, F., Berraondo, P., Etxeberria, I., Frederick, J., Sahin, U., Gilboa, E., & Melero, I.
- Affiliations
- Centro de Investigación Médica Aplicada (ES)
- Navarre Institute of Health Research (ES)
- Moderna Therapeutics (United States) (US)
- University of Miami (US)
- Corresponding author
- Melero, Ignacio
- Venue
- Nature Reviews Drug Discovery
- Published
- 2018-09-07
- Volume
- 17
- Issue
- 10
- Pages
- 751-767
- ISSN
- 1474-1776 (ISSN-L)
- 1474-1784
- OpenAlex
- W2889813782
- Cited by
- 229
- References
- 179
- Citations by year
- 2026: 11 · 2025: 27 · 2024: 24 · 2023: 39 · 2022: 40 · 2021: 33 · 2020: 27 · 2019: 27 · 2018: 1
- FWCI
- 2.25
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature Reviews Drug Discovery (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › Immunotherapy and Immune Responses
- Health Sciences › Medicine › Oncology › Cancer Immunotherapy and Biomarkers
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Interference and Gene Delivery
- Keywords
- cancer immunotherapy, RNA vaccines, neoantigens, mRNA vaccines, RNA interference, RNA aptamers, immunomodulation, innate immune activation, post-transcriptional regulation, cancer vaccines, combination immunotherapy
- MeSH terms
- Animals, Humans, Immunotherapy, Neoplasms, RNA, Cancer Vaccines, RNA Interference, Immunomodulation
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