Evidence map›Paper›PMID 30180944›Full record

ArticleCytotherapy2018

Manufacturing development and clinical production of NKG2D chimeric antigen receptor-expressing T cells for autologous adoptive cell therapy.

Joana M Murad, Susanne H Baumeister, Lillian Werner, Heather Daley, Hélène Trébéden-Negre, Jake Reder, Charles L Sentman, David Gilham, Frederic Lehmann, Sarah Snykers and 7 more

Registry-linked trialAbstract read
In one paragraph

Article in Cytotherapy, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT02203825 (A Phase 1 Study of Chimeric Antigen Receptor Modified T-cells Targeting NKG2D-Ligands in Patients With Acute Myeloid Leukemia), which is not on this map. Cited by 36 papers.

0numbers the graph read from it
0cells of the map it votes in
36citing 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.

NCT02203825 phase1completednot on this map

A Phase 1 Study of Chimeric Antigen Receptor Modified T-cells Targeting NKG2D-Ligands in Patients With Acute Myeloid Leukemia (AML)/Advanced Myelodysplastic Syndrome (MDS-RAEB) and Multiple Myeloma.

TypeinterventionalSponsorCelyad Oncology SARan2015 to 2018Enrolled12ConditionsAcute Myeloid Leukemia, Myelodysplastic Syndrome, Multiple MyelomaArmsCM-CS1 T-cell infusion
3 · Its place in the literature

Who cites it

36 citing papers in PubMed.

  1. Review
  2. Article
  3. CAR-T cell therapy for cancer: current challenges and future directions.Signal transduction and targeted therapy · 2025
    Review
  4. Review
  5. Review
  6. Review
  7. Article
  8. Review
  9. Review
  10. Review
  11. Review
  12. Review
  13. Review
  14. Article
  15. Review
  16. Review
  17. Article
  18. Review
  19. Article
  20. CAR-T Cell Therapy for Acute Myeloid Leukemia: Preclinical Rationale, Current Clinical Progress, and Barriers to Success.BioDrugs : clinical immunotherapeutics, biopharmaceuticals and gene therapy · 2021
    Review
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

17 authors.

Joana M MuradCeldara Medical, LLC, Lebanon, New Hampshire, USA.
Susanne H BaumeisterHarvard Medical School, Boston, Massachusetts, USA; Dana-Farber Cancer Institute, Boston, Massachusetts, USA; Boston Children's Hospital, Boston, Massachusetts, USA.
Lillian WernerHarvard Medical School, Boston, Massachusetts, USA.
Heather DaleyDana-Farber Cancer Institute, Boston, Massachusetts, USA.
Hélène Trébéden-NegreDana-Farber Cancer Institute, Boston, Massachusetts, USA.
Jake RederCeldara Medical, LLC, Lebanon, New Hampshire, USA.
Charles L SentmanGeisel School of Medicine at Dartmouth, Lebanon, New Hampshire, USA.
David GilhamCelyad SA, Mont Saint Guibert, Belgium.
Frederic LehmannCelyad SA, Mont Saint Guibert, Belgium.
Sarah SnykersCelyad SA, Mont Saint Guibert, Belgium.
Marie-Louise SentmanGeisel School of Medicine at Dartmouth, Lebanon, New Hampshire, USA.
Terri WadeCeldara Medical, LLC, Lebanon, New Hampshire, USA.
Adam SchmuckerCeldara Medical, LLC, Lebanon, New Hampshire, USA.
Michael W FangerCeldara Medical, LLC, Lebanon, New Hampshire, USA; Geisel School of Medicine at Dartmouth, Lebanon, New Hampshire, USA.
Glenn DranoffNovartis Institutes for BioMedical Research, Cambridge, Massachusetts, USA.
Jerome RitzHarvard Medical School, Boston, Massachusetts, USA; Dana-Farber Cancer Institute, Boston, Massachusetts, USA.
Sarah NikiforowHarvard Medical School, Boston, Massachusetts, USA; Dana-Farber Cancer Institute, Boston, Massachusetts, USA. Electronic address: sarah_nikiforow@dfci.harvard.edu.

Funding

ChNKG2D-Targeted Cellular Cancer Therapy: Phase I Clinical TrialR44HL099217 · NHLBI · CELDARA MEDICAL, LLC · PI FANGER, MICHAEL W · 2012 to 2013
$3.2M
NHLBI NIH HHS R44 HL099217
6 · The paper itself

Abstract

BACKGROUND

aimsAdoptive cell therapy employing natural killer group 2D (NKG2D) chimeric antigen receptor (CAR)-modified T cells has demonstrated preclinical efficacy in several model systems, including hematological and solid tumors. We present comprehensive data on manufacturing development and clinical production of autologous NKG2D CAR T cells for treatment of acute myeloid leukemia and multiple myeloma (ClinicalTrials.gov Identifier: NCT02203825). An NKG2D CAR was generated by fusing native full-length human NKG2D to the human CD3ζ cytoplasmic signaling domain. NKG2D naturally associates with native costimulatory molecule DAP10, effectively generating a second-generation CAR against multiple ligands upregulated during malignant transformation including MIC-A, MIC-B and the UL-16 binding proteins.

methodsCAR T cells were infused fresh after a 9-day process wherein OKT3-activated T cells were genetically modified with replication-defective gamma-retroviral vector and expanded ex vivo for 5 days with recombinant human interleukin-2.

resultsDespite sizable interpatient variation in originally collected cells, release criteria, including T-cell expansion and purity (median 98%), T-cell transduction (median 66% CD8

conclusionsThe process resulted in production of required cell doses for the first-in-human phase I NKG2D CAR T clinical trial and provides a robust, flexible base for further optimization of NKG2D CAR T-cell manufacturing.

Indexed as

Immunotherapy, AdoptiveCell Line, TumorCell ProliferationClinical Trials as TopicCytokinesHumansLigandsNK Cell Lectin-Like Receptor Subfamily KPhenotypeReceptors, Antigen, T-CellReceptors, Chimeric AntigenT-LymphocytesTransplantation, AutologousCytokinesLigandsNK Cell Lectin-Like Receptor Subfamily KReceptors, Antigen, T-CellReceptors, Chimeric Antigenacute myeloid leukemiaCAR Tchimeric antigen receptorgamma retrovirusGood manufacturing practice cell therapymultiple myelomaNKG2D

Identifiers

PMID30180944
PMCPMC6127861

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Registered trials

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.