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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  • 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)

Readers on

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

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 434 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 467 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
United States 8 2%
Germany 6 1%
United Kingdom 6 1%
France 2 <1%
Italy 2 <1%
Finland 2 <1%
Spain 2 <1%
Australia 1 <1%
Brazil 1 <1%
Other 9 2%
Unknown 428 92%

Demographic breakdown

Readers by professional status Count As %
Student > Ph. D. Student 138 30%
Researcher 113 24%
Student > Master 62 13%
Student > Bachelor 44 9%
Student > Doctoral Student 26 6%
Other 84 18%
Readers by discipline Count As %
Agricultural and Biological Sciences 194 42%
Medicine and Dentistry 75 16%
Biochemistry, Genetics and Molecular Biology 65 14%
Immunology and Microbiology 43 9%
Chemistry 35 7%
Other 55 12%

Attention Score in Context

This research output has an Altmetric Attention Score of 1816. 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 05 February 2017.
All research outputs
#300
of 7,410,780 outputs
Outputs from Nature
#92
of 45,431 outputs
Outputs of similar age
#29
of 264,662 outputs
Outputs of similar age from Nature
#5
of 980 outputs
Altmetric has tracked 7,410,780 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 45,431 research outputs from this source. They typically receive a lot more attention than average, with a mean Attention Score of 69.7. 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 264,662 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 980 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.