Evidence map›Paper›PMID 27281205›Full record

ArticleNature2016

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

Lena M Kranz, Mustafa Diken, Heinrich Haas, Sebastian Kreiter, Carmen Loquai, Kerstin C Reuter, Martin Meng, Daniel Fritz, Fulvia Vascotto, Hossam Hefesha and 18 more

Abstract read
PubMed Publisher
In one paragraph

Article in Nature, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 958 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
958citing papers in PubMed, 1 pooled it
62.3field-weighted citation impact, top 1% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

958 citing papers in PubMed, 1 synthesis or guideline pooled it, 1,692 citations in OpenAlex.

  1. Pooled it
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  15. Therapeutic vaccines for NSCLC: From mechanisms to clinical translation.Chinese medical journal pulmonary and critical care medicine · 2026
    Review
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898 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

28 authors at 5 institutions in 1 country.

Lena M KranzTRON-Translational Oncology at the University Medical Center of the Johannes Gutenberg University gGmbH, Freiligrathstr. 12, Mainz 55131, Germany.
Mustafa DikenTRON-Translational Oncology at the University Medical Center of the Johannes Gutenberg University gGmbH, Freiligrathstr. 12, Mainz 55131, Germany.
Heinrich HaasBiopharmaceutical New Technologies (BioNTech) Corporation, An der Goldgrube 12, Mainz 55131, Germany.
Sebastian KreiterTRON-Translational Oncology at the University Medical Center of the Johannes Gutenberg University gGmbH, Freiligrathstr. 12, Mainz 55131, Germany.
Carmen LoquaiDepartment of Dermatology, University Medical Center of the Johannes Gutenberg University, Langenbeckstr. 1, Mainz 55131, Germany.
Kerstin C ReuterBiopharmaceutical New Technologies (BioNTech) Corporation, An der Goldgrube 12, Mainz 55131, Germany.
Martin MengBiopharmaceutical New Technologies (BioNTech) Corporation, An der Goldgrube 12, Mainz 55131, Germany.
Daniel FritzBiopharmaceutical New Technologies (BioNTech) Corporation, An der Goldgrube 12, Mainz 55131, Germany.
Fulvia VascottoTRON-Translational Oncology at the University Medical Center of the Johannes Gutenberg University gGmbH, Freiligrathstr. 12, Mainz 55131, Germany.
Hossam HefeshaBiopharmaceutical New Technologies (BioNTech) Corporation, An der Goldgrube 12, Mainz 55131, Germany.
Christian GrunwitzResearch Center for Immunotherapy (FZI), University Medical Center at the Johannes Gutenberg University, Langenbeckstr. 1, Mainz 55131, Germany.
Mathias VormehrResearch Center for Immunotherapy (FZI), University Medical Center at the Johannes Gutenberg University, Langenbeckstr. 1, Mainz 55131, Germany.
Yves HüsemannBiopharmaceutical New Technologies (BioNTech) Corporation, An der Goldgrube 12, Mainz 55131, Germany.
Abderraouf SelmiTRON-Translational Oncology at the University Medical Center of the Johannes Gutenberg University gGmbH, Freiligrathstr. 12, Mainz 55131, Germany.
Andreas N KuhnBiopharmaceutical New Technologies (BioNTech) Corporation, An der Goldgrube 12, Mainz 55131, Germany.
Janina BuckBiopharmaceutical New Technologies (BioNTech) Corporation, An der Goldgrube 12, Mainz 55131, Germany.
Evelyna DerhovanessianBiopharmaceutical New Technologies (BioNTech) Corporation, An der Goldgrube 12, Mainz 55131, Germany.
Richard RaeTRON-Translational Oncology at the University Medical Center of the Johannes Gutenberg University gGmbH, Freiligrathstr. 12, Mainz 55131, Germany.
Sebastian AttigTRON-Translational Oncology at the University Medical Center of the Johannes Gutenberg University gGmbH, Freiligrathstr. 12, Mainz 55131, Germany.
Jan DiekmannBiopharmaceutical New Technologies (BioNTech) Corporation, An der Goldgrube 12, Mainz 55131, Germany.
Robert A JabulowskyBiopharmaceutical New Technologies (BioNTech) Corporation, An der Goldgrube 12, Mainz 55131, Germany.
Sandra HeeschBiopharmaceutical New Technologies (BioNTech) Corporation, An der Goldgrube 12, Mainz 55131, Germany.
Jessica HasselDepartment of Dermatology, Heidelberg University Hospital, Im Neuenheimer Feld 440, 69120 Heidelberg, Germany.
Peter LangguthInstitute of Pharmacy and Biochemistry, Johannes Gutenberg University, Germany, Langenbeckstr. 1, Mainz 55131, Germany.
Stephan GrabbeDepartment of Dermatology, University Medical Center of the Johannes Gutenberg University, Langenbeckstr. 1, Mainz 55131, Germany.
Christoph HuberTRON-Translational Oncology at the University Medical Center of the Johannes Gutenberg University gGmbH, Freiligrathstr. 12, Mainz 55131, Germany.
Özlem TüreciCluster for Individualized Immune Intervention, Kupferbergterasse 19, Mainz 55116, Germany.
Ugur SahinTRON-Translational Oncology at the University Medical Center of the Johannes Gutenberg University gGmbH, Freiligrathstr. 12, Mainz 55131, Germany.
BioNTech (Germany) · DEJohannes Gutenberg University Mainz · DEUniversity Medical Center of the Johannes Gutenberg University Mainz · DECentre for Individualised Infection Medicine · DEUniversity Hospital Heidelberg · DE

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

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.

Indexed as

Administration, IntravenousAnimalsAntigen PresentationAntigens, NeoplasmAntigens, ViralAutoantigensCancer VaccinesClinical Trials, Phase I as TopicDendritic CellsDisease Models, AnimalDrug CarriersFemaleHumansImmunotherapyInterferon Type ILymphocyte ActivationAntigens, NeoplasmAntigens, ViralAutoantigensCancer VaccinesDrug CarriersInterferon Type IMembrane GlycoproteinsRNATlr7 protein, mouseToll-Like Receptor 7

Identifiers

PMID27281205
OpenAlexW2412158473

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.