Evidence map›Paper›PMID 26275446›Full record

ArticleCancer immunology, immunotherapy : CII2015

Protamine-stabilized RNA as an ex vivo stimulant of primary human dendritic cell subsets.

Annette E Sköld, Jasper J P van Beek, Simone P Sittig, Ghaith Bakdash, Jurjen Tel, Gerty Schreibelt, I Jolanda M de Vries

Open access · hybridAbstract read
In one paragraph

Article in Cancer immunology, immunotherapy : CII, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.

0numbers the graph read from it
0cells of the map it votes in
30citing papers in PubMed
2.2field-weighted citation impact, top 12% 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

30 citing papers in PubMed, 46 citations in OpenAlex.

  1. Trial
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  7. Review
  8. Intratumoral administration of CD1c (BDCA-1)Journal for immunotherapy of cancer · 2022
    Article
  9. Article
  10. Formulation and Delivery Technologies for mRNA Vaccines.Current topics in microbiology and immunology · 2022
    Article
  11. Advances in mRNA vaccines.International review of cell and molecular biology · 2022
    Review
  12. Review
  13. Use of Protamine in Nanopharmaceuticals-A Review.Nanomaterials (Basel, Switzerland) · 2021
    Review
  14. Article
  15. Review
  16. Article
  17. Article
  18. The Current Status of COVID-19 Vaccines.Frontiers in genome editing · 2020
    Review
  19. Health-related quality of life analysis in stage III melanoma patients treated with adjuvant dendritic cell therapy.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2019
    Article
  20. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

7 authors at 2 institutions in 2 countries.

Annette E SköldDepartment of Tumor Immunology, Radboud Institute for Molecular Life Sciences, Radboud University Medical Centre, Nijmegen, The Netherlands.ORCID http://orcid.org/0000-0002-5309-8860
Jasper J P van BeekDepartment of Tumor Immunology, Radboud Institute for Molecular Life Sciences, Radboud University Medical Centre, Nijmegen, The Netherlands.
Simone P SittigDepartment of Tumor Immunology, Radboud Institute for Molecular Life Sciences, Radboud University Medical Centre, Nijmegen, The Netherlands.
Ghaith BakdashDepartment of Tumor Immunology, Radboud Institute for Molecular Life Sciences, Radboud University Medical Centre, Nijmegen, The Netherlands.
Jurjen TelDepartment of Tumor Immunology, Radboud Institute for Molecular Life Sciences, Radboud University Medical Centre, Nijmegen, The Netherlands.
Gerty SchreibeltDepartment of Tumor Immunology, Radboud Institute for Molecular Life Sciences, Radboud University Medical Centre, Nijmegen, The Netherlands.
I Jolanda M de VriesDepartment of Tumor Immunology, Radboud Institute for Molecular Life Sciences, Radboud University Medical Centre, Nijmegen, The Netherlands. Jolanda.deVries@radboudumc.nl.
Radboud University Nijmegen · NLKarolinska University Hospital · SE

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Dendritic cells (DCs) are key in connecting innate and adaptive immunity. Their potential in inducing specific immune responses has made them interesting targets for immunotherapeutic approaches. Our research group was the first to exploit the naturally occurring myeloid DCs (mDCs) and plasmacytoid DCs (pDCs) in therapeutic vaccination trials against melanoma. To develop primary DC subsets as an optimal vaccine, the identification of a clinically applicable adjuvant activating both subsets is required. Although the expression of pathogen recognition receptors differs distinctly between the DC subsets, both pDCs and mDCs can respond to single-stranded RNA (ssRNA) via Toll-like receptors 7 and 8, respectively. Since ssRNA is easily degraded by RNases, we stabilized anionic RNA by complexing it with the positively charged protein protamine. This leads to the formation of protamine-RNA complexes with varying features depending on ionic content. We subsequently investigated the immunostimulatory effect of complexes that formed various salt concentrations on purified DC subsets. Both mDCs and pDCs upregulated maturation markers and produced pro-inflammatory cytokines in a dose-dependent way to the protamine-RNA complexes. This was dependent on endosomal acidification and correlated partly with the uptake of protamine-RNA complexes. Furthermore, both DC subsets induced T cell proliferation and IFN gamma secretion in a beneficial ratio to IL-10. These results indicate that protamine-RNA complexes can be used to stimulate human mDC and pDC ex vivo for use in immunotherapeutic settings.

Indexed as

Adjuvants, ImmunologicCells, CulturedCytokinesDendritic CellsDose-Response Relationship, DrugEndosomesHumansInterferon-gammaLymphocyte ActivationProtaminesRNARNA StabilitySodium ChlorideToll-Like ReceptorsAdjuvants, ImmunologicCytokinesInterferon-gammaProtaminesRNASodium ChlorideToll-Like ReceptorsAdjuvantsGMPImmunotherapymDCpDCTLR

Identifiers

PMID26275446
PMCPMC4612318
OpenAlexW2125126641

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.