Evidence map›Paper›PMID 25999171›Full record

ArticleScientific reports2015

Microfluidic squeezing for intracellular antigen loading in polyclonal B-cells as cellular vaccines.

Gregory Lee Szeto, Debra Van Egeren, Hermoon Worku, Armon Sharei, Brian Alejandro, Clara Park, Kirubel Frew, Mavis Brefo, Shirley Mao, Megan Heimann and 3 more

Abstract read
In one paragraph

Article in Scientific reports, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 54 papers.

0numbers the graph read from it
0cells of the map it votes in
54citing papers in PubMed
–field-weighted citation impact
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

54 citing papers in PubMed.

  1. Article
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  3. Article
  4. Adoptively transferred macrophages for cancer immunotherapy.Journal for immunotherapy of cancer · 2025
    Article
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  6. A small-molecule carrier for the intracellular delivery of a membrane-impermeable protein with retained bioactivity.Proceedings of the National Academy of Sciences of the United States of America · 2024
    Article
  7. Article
  8. Review
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  14. Article
  15. Article
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  17. Review
  18. Review
  19. Article
  20. Micromotor-based localized electroporation and gene transfection of mammalian cells.Proceedings of the National Academy of Sciences of the United States of America · 2021
    Article
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

13 authors.

Gregory Lee Szeto1] Department of Materials Science &Engineering, MIT [2] Department of Biological Engineering, MIT [3] David. H. Koch Institute for Integrative Cancer Research, MIT [4] The Ragon Institute of Harvard, MIT, and MGH.
Debra Van EgerenDepartment of Biological Engineering, MIT.
Hermoon WorkuDepartment of Biology, MIT.
Armon Sharei1] David. H. Koch Institute for Integrative Cancer Research, MIT [2] Department of Chemical Engineering, MIT [3] The Ragon Institute of Harvard, MIT, and MGH.
Brian AlejandroDepartment of Chemical Engineering, MIT.
Clara ParkDepartment of Biological Engineering, MIT.
Kirubel FrewThe Ragon Institute of Harvard, MIT, and MGH.
Mavis BrefoDepartment of Materials Science &Engineering, MIT.
Shirley MaoDepartment of Chemical Engineering, MIT.
Megan HeimannDavid. H. Koch Institute for Integrative Cancer Research, MIT.
Robert Langer1] David. H. Koch Institute for Integrative Cancer Research, MIT [2] Department of Chemical Engineering, MIT.
Klavs JensenDepartment of Chemical Engineering, MIT.
Darrell J Irvine1] Department of Materials Science &Engineering, MIT [2] Department of Biological Engineering, MIT [3] David. H. Koch Institute for Integrative Cancer Research, MIT [4] The Ragon Institute of Harvard, MIT, and MGH [5] Howard Hughes Medical Institute.

Funding

VIRUS PRODUCTION COREP30CA014051 · NCI · MASSACHUSETTS INSTITUTE OF TECHNOLOGY · PI Jacqueline A. Lees · 1985 to 2026
$93.9M
High throughput microfluidic intracellular delivery platformR01GM101420 · NIGMS · MASSACHUSETTS INSTITUTE OF TECHNOLOGY · PI ANDERSON, DANIEL G, JENSEN, KLAVS F · 2013 to 2016
$2.1M
Modulating AhR in tumor and lymphoid microenvironments via local drug deliveryF32CA180586 · NCI · MASSACHUSETTS INSTITUTE OF TECHNOLOGY · PI SZETO, GREGORY LEE · 2013 to 2014
$107k
Howard Hughes Medical InstituteNCI NIH HHS #1F32CA180586NCI NIH HHS F32 CA180586NCI NIH HHS P30 CA014051NCI NIH HHS P30-CA14051NIGMS NIH HHS R01 GM101420
6 · The paper itself

Abstract

B-cells are promising candidate autologous antigen-presenting cells (APCs) to prime antigen-specific T-cells both in vitro and in vivo. However to date, a significant barrier to utilizing B-cells as APCs is their low capacity for non-specific antigen uptake compared to "professional" APCs such as dendritic cells. Here we utilize a microfluidic device that employs many parallel channels to pass single cells through narrow constrictions in high throughput. This microscale "cell squeezing" process creates transient pores in the plasma membrane, enabling intracellular delivery of whole proteins from the surrounding medium into B-cells via mechano-poration. We demonstrate that both resting and activated B-cells process and present antigens delivered via mechano-poration exclusively to antigen-specific CD8(+)T-cells, and not CD4(+)T-cells. Squeezed B-cells primed and expanded large numbers of effector CD8(+)T-cells in vitro that produced effector cytokines critical to cytolytic function, including granzyme B and interferon-γ. Finally, antigen-loaded B-cells were also able to prime antigen-specific CD8(+)T-cells in vivo when adoptively transferred into mice. Altogether, these data demonstrate crucial proof-of-concept for mechano-poration as an enabling technology for B-cell antigen loading, priming of antigen-specific CD8(+)T-cells, and decoupling of antigen uptake from B-cell activation.

Indexed as

AnimalsAntigensB7-2 AntigenB-LymphocytesCD40 AntigensCD8-Positive T-LymphocytesCell Culture TechniquesCell ProliferationCells, CulturedCytokinesInterferon-gammaLymphocyte ActivationMiceMice, Inbred C57BLMicrofluidic Analytical TechniquesStress, MechanicalAntigensB7-2 AntigenCD40 AntigensCytokinesInterferon-gammaVaccines

Identifiers

PMID25999171
PMCPMC4441198

What OpenQuestion holds

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Registered trials

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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.