Evidence map›Paper›PMID 29535850›Full record

ArticleJournal of extracellular vesicles2018

Scalable, cGMP-compatible purification of extracellular vesicles carrying bioactive human heterodimeric IL-15/lactadherin complexes.

Dionysios C Watson, Bryant C Yung, Cristina Bergamaschi, Bhabadeb Chowdhury, Jenifer Bear, Dimitris Stellas, Aizea Morales-Kastresana, Jennifer C Jones, Barbara K Felber, Xiaoyuan Chen and 1 more

Open access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Journal of extracellular vesicles, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 105 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
105citing papers in PubMed, 1 pooled it
4.9field-weighted citation impact, top 4% 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

105 citing papers in PubMed, 1 synthesis or guideline pooled it, 171 citations in OpenAlex.

  1. Pooled it
  2. Trial
  3. Article
  4. Review
  5. Article
  6. Article
  7. Review
  8. Review
  9. Review
  10. Article
  11. Review
  12. Article
  13. Review
  14. Article
  15. Review
  16. Review
  17. 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
  18. Article
  19. Review
  20. Article

45 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

11 authors at 3 institutions in 1 country.

Dionysios C WatsonHuman Retrovirus Section, Vaccine Branch, Center for Cancer Research, National Cancer Institute at Frederick, Frederick, MD, USA.ORCID 0000-0002-9146-5641
Bryant C YungLaboratory of Molecular Imaging and Nanomedicine, National Institute of Biomedical Imaging and Bioengineering, National Institutes of Health, Bethesda, MD, USA.ORCID 0000-0003-2690-6778
Cristina BergamaschiHuman Retrovirus Pathogenesis Section, Vaccine Branch, Center for Cancer Research, National Cancer Institute at Frederick, Frederick, MD, USA.ORCID 0000-0003-1030-2662
Bhabadeb ChowdhuryHuman Retrovirus Section, Vaccine Branch, Center for Cancer Research, National Cancer Institute at Frederick, Frederick, MD, USA.ORCID 0000-0001-6308-7893
Jenifer BearHuman Retrovirus Pathogenesis Section, Vaccine Branch, Center for Cancer Research, National Cancer Institute at Frederick, Frederick, MD, USA.ORCID 0000-0001-5065-6081
Dimitris StellasHuman Retrovirus Section, Vaccine Branch, Center for Cancer Research, National Cancer Institute at Frederick, Frederick, MD, USA.ORCID 0000-0002-7787-3921
Aizea Morales-KastresanaVaccine Branch, Center for Cancer Research, National Cancer Institute, Bethesda, MD, USA.ORCID 0000-0003-1401-9805
Jennifer C JonesVaccine Branch, Center for Cancer Research, National Cancer Institute, Bethesda, MD, USA.ORCID 0000-0002-9488-7719
Barbara K FelberHuman Retrovirus Pathogenesis Section, Vaccine Branch, Center for Cancer Research, National Cancer Institute at Frederick, Frederick, MD, USA.ORCID 0000-0001-8925-8128
Xiaoyuan ChenLaboratory of Molecular Imaging and Nanomedicine, National Institute of Biomedical Imaging and Bioengineering, National Institutes of Health, Bethesda, MD, USA.ORCID 0000-0002-9622-0870
George N PavlakisHuman Retrovirus Section, Vaccine Branch, Center for Cancer Research, National Cancer Institute at Frederick, Frederick, MD, USA.ORCID 0000-0002-4027-4036
Frederick National Laboratory for Cancer Research · USNational Cancer Institute · USNational Institutes of Health · US

Funding

Laboratory of Molecular Imaging and NanomedicineZIAEB000073 · NIBIB · NATIONAL INSTITUTE OF BIOMEDICAL IMAGING AND BIOENGINEERING · PI CHEN, XIAOYUAN · 2010 to 2020
$32.8M
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
6 · The paper itself

Abstract

The development of extracellular vesicles (EV) for therapeutic applications is contingent upon the establishment of reproducible, scalable, and high-throughput methods for the production and purification of clinical grade EV. Methods including ultracentrifugation (U/C), ultrafiltration, immunoprecipitation, and size-exclusion chromatography (SEC) have been employed to isolate EV, each facing limitations such as efficiency, particle purity, lengthy processing time, and/or sample volume. We developed a cGMP-compatible method for the scalable production, concentration, and isolation of EV through a strategy involving bioreactor culture, tangential flow filtration (TFF), and preparative SEC. We applied this purification method for the isolation of engineered EV carrying multiple complexes of a novel human immunostimulatory cytokine-fusion protein, heterodimeric IL-15 (hetIL-15)/lactadherin. HEK293 cells stably expressing the fusion cytokine were cultured in a hollow-fibre bioreactor. Conditioned medium was collected and EV were isolated comparing three procedures: U/C, SEC, or TFF + SEC. SEC demonstrated comparable particle recovery, size distribution, and hetIL-15 density as U/C purification. Relative to U/C, SEC preparations achieved a 100-fold reduction in ferritin concentration, a major protein-complex contaminant. Comparative proteomics suggested that SEC additionally decreased the abundance of cytoplasmic proteins not associated with EV. Combination of TFF and SEC allowed for bulk processing of large starting volumes, and resulted in bioactive EV, without significant loss in particle yield or changes in size, morphology, and hetIL-15/lactadherin density. Taken together, the combination of bioreactor culture with TFF + SEC comprises a scalable, efficient method for the production of highly purified, bioactive EV carrying hetIL-15/lactadherin, which may be useful in targeted cancer immunotherapy approaches.

Indexed as

bioreactorclinical gradeExosomesimmunotherapyinterleukin-15Kenneth W. Witwer, Johns Hopkins University, USAlactadherinlarge scalepurificationsize-exclusion chromatographytangential flow filtration

Identifiers

PMID29535850
PMCPMC5844027
OpenAlexW2790088751

What OpenQuestion holds

Textmetadata
LicenceCC0
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.