Evidence map›Paper›PMID 27210719›Full record

ArticleCytotherapy2016

Myeloid cells in peripheral blood mononuclear cell concentrates inhibit the expansion of chimeric antigen receptor T cells.

David F Stroncek, Jiaqiang Ren, Daniel W Lee, Minh Tran, Sue Ellen Frodigh, Marianna Sabatino, Hanh Khuu, Melinda S Merchant, Crystal L Mackall

Abstract readClinical Trial, Phase I
In one paragraph

Article in Cytotherapy, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 89 papers.

0numbers the graph read from it
0cells of the map it votes in
89citing 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

89 citing papers in PubMed.

  1. Trial
  2. Trial
  3. Trial
  4. Article
  5. Review
  6. Article
  7. Review
  8. Article
  9. Article
  10. Article
  11. Review
  12. Article
  13. Review
  14. Article
  15. Article
  16. Review
  17. Review
  18. Harnessing myeloid cells in cancer.Molecular cancer · 2025
    Review
  19. Review
  20. Review

29 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

9 authors.

David F StroncekCell Processing Section, Department of Transfusion Medicine, National Institutes of Health Clinical Center, Bethesda, MD, USA. Electronic address: dstroncek@cc.nih.gov.
Jiaqiang RenCell Processing Section, Department of Transfusion Medicine, National Institutes of Health Clinical Center, Bethesda, MD, USA.
Daniel W LeePediatric Oncology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.
Minh TranCell Processing Section, Department of Transfusion Medicine, National Institutes of Health Clinical Center, Bethesda, MD, USA.
Sue Ellen FrodighCell Processing Section, Department of Transfusion Medicine, National Institutes of Health Clinical Center, Bethesda, MD, USA.
Marianna SabatinoCell Processing Section, Department of Transfusion Medicine, National Institutes of Health Clinical Center, Bethesda, MD, USA.
Hanh KhuuCell Processing Section, Department of Transfusion Medicine, National Institutes of Health Clinical Center, Bethesda, MD, USA.
Melinda S MerchantPediatric Oncology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.
Crystal L MackallPediatric Oncology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.

Funding

Develop novel assays for assessing cellular and gene therapiesZIACL002119 · CLC · CLINICAL CENTER · PI STRONCEK, DAVID · 2010 to 2025
$0k
Development of novel cell and gene therapiesZIACL002120 · CLC · CLINICAL CENTER · PI STRONCEK, DAVID · 2009 to 2025
$0k
Intramural NIH HHS ZIA CL002119
6 · The paper itself

Abstract

BACKGROUND

aimsAutologous chimeric antigen receptor (CAR) T-cell therapies have shown promising clinical outcomes, but T-cell yields have been variable. CD19- and GD2-CAR T-cell manufacturing records were reviewed to identify sources of variability.

methodsCD19-CAR T cells were used to treat 43 patients with acute lymphocytic leukemia or lymphoma and GD2-CAR T cells to treat eight patients with osteosarcoma and three with neuroblastoma. Both types of CAR T cells were manufactured using autologous peripheral blood mononuclear cells (PBMC) concentrates and anti-CD3/CD28 beads for T-cell enrichment and simulation.

resultsA comparison of the first 6 GD2- and the first 22 CD19-CAR T-cell products manufactured revealed that GD2-CAR T-cell products contained fewer transduced cells than CD19-CAR T-cell products (147 ± 102 × 10(6) vs 1502 ± 1066 × 10(6); P = 0.0059), and their PBMC concentrates contained more monocytes (31.4 ± 12.4% vs 18.5 ± 13.7%; P = 0.019). Among the first 28 CD19-CAR T-cell products manufactured, four had poor expansion yielding less than 1 × 10(6) transduced T cells per kilogram. When PBMC concentrates from these four patients were compared with the 24 others, PBMC concentrates of poorly expanding products contained greater quantities of monocytes (39.8 ± 12.9% vs. 15.3 ± 10.8%, P = 0.0014). Among the patients whose CD19-CAR T cells expanded poorly, manufacturing for two patients was repeated using cryopreserved PBMC concentrates but incorporating a monocyte depleting plastic adherence step, and an adequate dose of CAR T cells was produced for both patients.

conclusionsVariability in CAR T-cell expansion is due, at least in part, to the contamination of the starting PBMC concentrates with monocytes.

Indexed as

Antigens, CD19Cell ProliferationChildHumansImmunotherapyLeukocytes, MononuclearMonocytesMyeloid CellsReceptors, Antigen, T-CellT-LymphocytesTransduction, GeneticYoung AdultAntigens, CD19Receptors, Antigen, T-Cellacute lymphocytic leukemiaadoptive cellular therapyCD19chimeric antigen receptor T cellsGD2osteosarcoma

Identifiers

PMID27210719
PMCPMC4898642

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.