Evidence map›Paper›PMID 27522254›Full record

ArticleBiomaterials2016

Efficient production and enhanced tumor delivery of engineered extracellular vesicles.

Dionysios C Watson, Defne Bayik, Avinash Srivatsan, Cristina Bergamaschi, Antonio Valentin, Gang Niu, Jenifer Bear, Mitchell Monninger, Mei Sun, Aizea Morales-Kastresana and 5 more

Open access · hybridAbstract read
In one paragraph

Article in Biomaterials, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 204 papers, 3 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
204citing papers in PubMed, 3 pooled it
11.7field-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

204 citing papers in PubMed, 3 syntheses or guidelines pooled it, 377 citations in OpenAlex.

  1. Pooled it
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  15. Designing nucleic acid-based therapeutics for cancer treatment: Updates on the state of the art.Molecular therapy : the journal of the American Society of Gene Therapy · 2026
    Review
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  19. [Stem cell therapy for premature ovarian insufficiency: a review of clinical evidence and therapeutic strategies].Zhejiang da xue xue bao. Yi xue ban = Journal of Zhejiang University. Medical sciences · 2025
    Review
  20. Review

144 more citing papers are in PubMed but not listed here.

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

15 authors at 6 institutions in 3 countries.

Dionysios C WatsonHuman Retrovirus Section, Vaccine Branch, Center for Cancer Research, National Cancer Institute at Frederick, Frederick, MD 21702, United States; Department of Medicine, University of Patras, Greece.
Defne BayikCancer and Inflammation Program, Center for Cancer Research, National Cancer Institute at Frederick, Frederick, MD 21702, United States; Department of Molecular Biology and Genetics, Bilkent University, Ankara, 06800 Turkey.
Avinash SrivatsanLaboratory of Molecular Imaging and Nanomedicine, National Institute of Biomedical Imaging and Bioengineering, National Institutes of Health, Bethesda, MD 20892, United States.
Cristina BergamaschiHuman Retrovirus Pathogenesis Section, Vaccine Branch, Center for Cancer Research, National Cancer Institute at Frederick, Frederick, MD 21702, United States.
Antonio ValentinHuman Retrovirus Section, Vaccine Branch, Center for Cancer Research, National Cancer Institute at Frederick, Frederick, MD 21702, United States.
Gang NiuLaboratory of Molecular Imaging and Nanomedicine, National Institute of Biomedical Imaging and Bioengineering, National Institutes of Health, Bethesda, MD 20892, United States.
Jenifer BearHuman Retrovirus Pathogenesis Section, Vaccine Branch, Center for Cancer Research, National Cancer Institute at Frederick, Frederick, MD 21702, United States.
Mitchell MonningerPathology Division, United States Army Medical Research Institute of Infectious Diseases, Frederick, MD 21702, United States.
Mei SunPathology Division, United States Army Medical Research Institute of Infectious Diseases, Frederick, MD 21702, United States.
Aizea Morales-KastresanaVaccine Branch, Center for Cancer Research, National Cancer Institute, Bethesda, MD 20892, United States.
Jennifer C JonesVaccine Branch, Center for Cancer Research, National Cancer Institute, Bethesda, MD 20892, United States.
Barbara K FelberHuman Retrovirus Pathogenesis Section, Vaccine Branch, Center for Cancer Research, National Cancer Institute at Frederick, Frederick, MD 21702, United States.
Xiaoyuan ChenLaboratory of Molecular Imaging and Nanomedicine, National Institute of Biomedical Imaging and Bioengineering, National Institutes of Health, Bethesda, MD 20892, United States.
Ihsan GurselDepartment of Molecular Biology and Genetics, Bilkent University, Ankara, 06800 Turkey.
George N PavlakisHuman Retrovirus Section, Vaccine Branch, Center for Cancer Research, National Cancer Institute at Frederick, Frederick, MD 21702, United States. Electronic address: George.pavlakis@nih.gov.
Frederick National Laboratory for Cancer Research · USNational Institutes of Health · USBilkent University · TRNational Cancer Institute · USUnited States Army Medical Research Institute of Infectious Diseases · USUniversity of Patras · GR

Funding

Heterodimeric IL-15 in Cancer ImmunotherapyZIABC010750 · NCI · DIVISION OF BASIC SCIENCES - NCI · PI PAVLAKIS, GEORGE N. · 2009 to 2022
$15.6M
Development and use of nanoFACS for analysis and sorting of nanoparticlesZIABC011502 · NCI · DIVISION OF BASIC SCIENCES - NCI · PI JONES, JENNIFER · 2013 to 2025
$8.6M
Novel Combinations of Radiation and ImmunotherapyZIABC011503 · NCI · DIVISION OF BASIC SCIENCES - NCI · PI JONES, JENNIFER · 2013 to 2025
$5.3M
Intramural NIH HHS ZIA BC010750
6 · The paper itself

Abstract

Extracellular vesicles (EV), including exosomes and microvesicles, are nano-sized intercellular communication vehicles that participate in a multitude of physiological processes. Due to their biological properties, they are also promising candidates for the systemic delivery of therapeutic compounds, such as cytokines, chemotherapeutic drugs, siRNAs and viral vectors. However, low EV production yield and rapid clearance of administered EV by liver macrophages limit their potential use as therapeutic vehicles. We have used a hollow-fiber bioreactor for the efficient production of bioactive EV bearing the heterodimeric cytokine complex Interleukin-15:Interleukin-15 receptor alpha. Bioreactor culture yielded ∼40-fold more EV per mL conditioned medium, as compared to conventional cell culture. Biophysical analysis and comparative proteomics suggested a more diverse population of EV in the bioreactor preparations, while serum protein contaminants were detectable only in conventional culture EV preparations. We also identified the Scavenger Receptor Class A family (SR-A) as a novel monocyte/macrophage uptake receptor for EV. In vivo blockade of SR-A with dextran sulfate dramatically decreased EV liver clearance in mice, while enhancing tumor accumulation. These findings facilitate development of EV therapeutic methods.

Indexed as

BioreactorsBatch Cell Culture TechniquesCell FractionationCells, CulturedEquipment DesignExtracellular VesiclesHEK293 CellsHumansMacrophagesNeoplasms, ExperimentalTissue EngineeringBiodistributionDextran sulfateDrug deliveryExosomesReticuloendothelial systemScavenger receptor

Identifiers

PMID27522254
PMCPMC7156278
OpenAlexW2466551530

What OpenQuestion holds

Textmetadata
LicenceTDM
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.