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Systemic RNA delivery to dendritic cells exploits antiviral defence for cancer immunotherapy

Overview of attention for article published in Nature, June 2016
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About this Attention Score

  • In the top 5% of all research outputs scored by Altmetric
  • High Attention Score compared to outputs of the same age (99th percentile)
  • High Attention Score compared to outputs of the same age and source (99th percentile)

Citations

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615 Dimensions

Readers on

mendeley
1353 Mendeley
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3 CiteULike
Title
Systemic RNA delivery to dendritic cells exploits antiviral defence for cancer immunotherapy
Published in
Nature, June 2016
DOI 10.1038/nature18300
Pubmed ID
Authors

Lena M. Kranz, Mustafa Diken, Heinrich Haas, Sebastian Kreiter, Carmen Loquai, Kerstin C. Reuter, Martin Meng, Daniel Fritz, Fulvia Vascotto, Hossam Hefesha, Christian Grunwitz, Mathias Vormehr, Yves Hüsemann, Abderraouf Selmi, Andreas N. Kuhn, Janina Buck, Evelyna Derhovanessian, Richard Rae, Sebastian Attig, Jan Diekmann, Robert A. Jabulowsky, Sandra Heesch, Jessica Hassel, Peter Langguth, Stephan Grabbe, Christoph Huber, Özlem Türeci, Ugur Sahin

Abstract

Lymphoid organs, in which antigen presenting cells (APCs) are in close proximity to T cells, are the ideal microenvironment for efficient priming and amplification of T-cell responses. However, the systemic delivery of vaccine antigens into dendritic cells (DCs) is hampered by various technical challenges. Here we show that DCs can be targeted precisely and effectively in vivo using intravenously administered RNA-lipoplexes (RNA-LPX) based on well-known lipid carriers by optimally adjusting net charge, without the need for functionalization of particles with molecular ligands. The LPX protects RNA from extracellular ribonucleases and mediates its efficient uptake and expression of the encoded antigen by DC populations and macrophages in various lymphoid compartments. RNA-LPX triggers interferon-α (IFNα) release by plasmacytoid DCs and macrophages. Consequently, DC maturation in situ and inflammatory immune mechanisms reminiscent of those in the early systemic phase of viral infection are activated. We show that RNA-LPX encoding viral or mutant neo-antigens or endogenous self-antigens induce strong effector and memory T-cell responses, and mediate potent IFNα-dependent rejection of progressive tumours. A phase I dose-escalation trial testing RNA-LPX that encode shared tumour antigens is ongoing. In the first three melanoma patients treated at a low-dose level, IFNα and strong antigen-specific T-cell responses were induced, supporting the identified mode of action and potency. As any polypeptide-based antigen can be encoded as RNA, RNA-LPX represent a universally applicable vaccine class for systemic DC targeting and synchronized induction of both highly potent adaptive as well as type-I-IFN-mediated innate immune mechanisms for cancer immunotherapy.

Twitter Demographics

The data shown below were collected from the profiles of 381 tweeters who shared this research output. Click here to find out more about how the information was compiled.

Mendeley readers

The data shown below were compiled from readership statistics for 1,353 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
United States 8 <1%
United Kingdom 6 <1%
Germany 4 <1%
Spain 3 <1%
France 2 <1%
Finland 2 <1%
Brazil 1 <1%
Australia 1 <1%
Italy 1 <1%
Other 5 <1%
Unknown 1320 98%

Demographic breakdown

Readers by professional status Count As %
Student > Ph. D. Student 331 24%
Researcher 283 21%
Student > Master 165 12%
Student > Bachelor 117 9%
Student > Doctoral Student 71 5%
Other 202 15%
Unknown 184 14%
Readers by discipline Count As %
Agricultural and Biological Sciences 258 19%
Biochemistry, Genetics and Molecular Biology 256 19%
Immunology and Microbiology 174 13%
Medicine and Dentistry 121 9%
Chemistry 90 7%
Other 244 18%
Unknown 210 16%

Attention Score in Context

This research output has an Altmetric Attention Score of 1853. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 09 June 2021.
All research outputs
#2,727
of 17,948,621 outputs
Outputs from Nature
#355
of 80,710 outputs
Outputs of similar age
#45
of 274,703 outputs
Outputs of similar age from Nature
#7
of 1,019 outputs
Altmetric has tracked 17,948,621 research outputs across all sources so far. Compared to these this one has done particularly well and is in the 99th percentile: it's in the top 5% of all research outputs ever tracked by Altmetric.
So far Altmetric has tracked 80,710 research outputs from this source. They typically receive a lot more attention than average, with a mean Attention Score of 91.3. This one has done particularly well, scoring higher than 99% of its peers.
Older research outputs will score higher simply because they've had more time to accumulate mentions. To account for age we can compare this Altmetric Attention Score to the 274,703 tracked outputs that were published within six weeks on either side of this one in any source. This one has done particularly well, scoring higher than 99% of its contemporaries.
We're also able to compare this research output to 1,019 others from the same source and published within six weeks on either side of this one. This one has done particularly well, scoring higher than 99% of its contemporaries.