Evidence map›Paper›PMID 28298232›Full record

ArticleJournal of translational medicine2017

Elutriated lymphocytes for manufacturing chimeric antigen receptor T cells.

David F Stroncek, Daniel W Lee, Jiaqiang Ren, Marianna Sabatino, Steven Highfill, Hanh Khuu, Nirali N Shah, Rosandra N Kaplan, Terry J Fry, Crystal L Mackall

Abstract readClinical Trial, Phase I
In one paragraph

Article in Journal of translational medicine, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 papers.

0numbers the graph read from it
0cells of the map it votes in
41citing 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

41 citing papers in PubMed.

  1. Trial
  2. Article
  3. Article
  4. Review
  5. CAR T Cell Nanosymbionts: Revealing the Boundless Potential of a New Dyad.International journal of molecular sciences · 2024
    Review
  6. Review
  7. Article
  8. Review
  9. Article
  10. CD8Journal for immunotherapy of cancer · 2023
    Article
  11. Review
  12. Article
  13. Article
  14. Phase I CAR-T Clinical Trials Review.Anticancer research · 2022
    Review
  15. Article
  16. Article
  17. Review
  18. Frontiers in immunology · 2022
    Article
  19. Article
  20. 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

10 authors.

David F StroncekCell Processing Section, Department of Transfusion Medicine, NIH Clinical Center, NIH, 10 Center Drive-MSC-1184, Building 10, Room 3C720, Bethesda, MD, 20892-1184, USA. dstroncek@cc.nih.gov.ORCID 0000-0001-5867-3265
Daniel W LeeDivision of Pediatric Hematology/Oncology, Department of Pediatrics, University of Virginia, Charlottesville, USA.
Jiaqiang RenCell Processing Section, Department of Transfusion Medicine, NIH Clinical Center, NIH, 10 Center Drive-MSC-1184, Building 10, Room 3C720, Bethesda, MD, 20892-1184, USA.
Marianna SabatinoCell Processing Section, Department of Transfusion Medicine, NIH Clinical Center, NIH, 10 Center Drive-MSC-1184, Building 10, Room 3C720, Bethesda, MD, 20892-1184, USA.
Steven HighfillCell Processing Section, Department of Transfusion Medicine, NIH Clinical Center, NIH, 10 Center Drive-MSC-1184, Building 10, Room 3C720, Bethesda, MD, 20892-1184, USA.
Hanh KhuuCell Processing Section, Department of Transfusion Medicine, NIH Clinical Center, NIH, 10 Center Drive-MSC-1184, Building 10, Room 3C720, Bethesda, MD, 20892-1184, USA.
Nirali N ShahPediatric Oncology Branch, Center for Cancer Research, National Cancer Center, NIH, Bethesda, USA.
Rosandra N KaplanPediatric Oncology Branch, Center for Cancer Research, National Cancer Center, NIH, Bethesda, USA.
Terry J FryPediatric Oncology Branch, Center for Cancer Research, National Cancer Center, NIH, Bethesda, USA.
Crystal L MackallParker Institute for Cancer Immunotherapy, Stanford University, Stanford, USA.

Funding

Optimizing the graft versus leukemia effect for pediatric ALLZIABC011295 · NCI · DIVISION OF BASIC SCIENCES - NCI · PI FRY, TERRY · 2010 to 2018
$4.8M
6 · The paper itself

Abstract

backgroundClinical trials of Chimeric Antigen Receptor (CAR) T cells manufactured from autologous peripheral blood mononuclear cell (PBMC) concentrates for the treatment of hematologic malignancies have been promising, but CAR T cell yields have been variable. This variability is due in part to the contamination of the PBMC concentrates with monocytes and granulocytes.

methodsCounter-flow elutriation allows for the closed system separation of lymphocytes from monocytes and granulocytes. We investigated the use of PBMC concentrates enriched for lymphocytes using elutriation for manufacturing 8 CD19- and 5 GD2-CAR T cell products.

resultsWhen compared to PBMC concentrates, lymphocyte-enriched elutriation fractions contained greater proportions of CD3+ and CD56+ cells and reduced proportions of CD14+ and CD15+ cells. All 13 CAR T cell products manufactured using the elutriated lymphocytes yielded sufficient quantities of transduced CAR T cells to meet clinical dose criteria. The GD2-CAR T cell products contained significantly more T cells and transduced T cells than the CD19-CAR T cell products. A comparison of the yields of CAR T cells produced from elutriated lymphocytes with the yields of CAR T cells previous produced from cells isolated from PBMC concentrates by anti-CD3/CD28 bead selection or by anti-CD3/CD28 bead selection plus plastic adherence found that greater quantities of GD2-CAR T cells were produced from elutriated lymphocytes, but not CD19-CAR T cells.

conclusionsEnrichment of PBMC concentrates for lymphocytes using elutriation increased the quantity of GD2-CAR T cells produced. These results provide further evidence that CAR T cell expansion is inhibited by monocytes and granulocytes.

Indexed as

Antigens, CDCell AdhesionChildHumansLymphocyte CountReceptors, Antigen, T-CellT-LymphocytesTransduction, GeneticYoung AdultAntigens, CDCD19-specific chimeric antigen receptorReceptors, Antigen, T-CellCancer immunotherapyCellular therapyChimeric antigen receptor T cellsElutriationMyeloid derived suppressor cellsPeripheral blood mononuclear cellsT cells

Identifiers

PMID28298232
PMCPMC5353875

What OpenQuestion holds

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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.