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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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Phosphorylation of AGO2 by TBK1 Promotes the Formation of Oncogenic miRISC in NSCLC
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“mRNA as a toolbox allows the delivery of complex chimeric proteins that are otherwise difficult to manufacture and purify.(6) For instance, in our case, the construction of a human reactive version would be feasible based on known sequences for the scFv of urelumab,(60) on the interspecies TGF-b crossreactivity of the…”
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“Furthermore, the immunostimulatory activity of RNAs has been recognized as a possible means to develop more potent RNA-based therapeutics and vaccine adjuvants [21,22].”
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“All well-known checkpoint molecules were developed as blocking aptamers and showed comparable effects to those of Abs in mouse models.(21,22) However, one of the biggest obstacles in the development of such an aptamer delivery system is its various and complex scaffold selection system.”
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“cancer immunotherapy featuring mRNA can revolutio-nise cancer treatment (Pastor et al. 2018).”
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Treatment of Experimental Autoimmune Encephalomyelitis by Sustained Delivery of Low-Dose IFN-α
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“This tempered activity would be favorable when using other delivery strategies, such as modified mRNA (37, 38) or s.”
BackgroundMethodEfficacy of LCMV-based cancer immunotherapies is unleashed by intratumoral injections of polyI:C
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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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