Evidence map›Paper›PMID 23741305›Full record

ArticlePloS one2013

Manufacture of clinical-grade CD19-specific T cells stably expressing chimeric antigen receptor using Sleeping Beauty system and artificial antigen presenting cells.

Harjeet Singh, Matthew J Figliola, Margaret J Dawson, Simon Olivares, Ling Zhang, Ge Yang, Sourindra Maiti, Pallavi Manuri, Vladimir Senyukov, Bipulendu Jena and 4 more

Registry-linked trialAbstract read
In one paragraph

Article in PloS one, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT05054257 (Safety and Efficacy of Anti-CD19 Chimeric Antigen Receptor-modified Autologous T Cells), which is not on this map. Cited by 93 papers.

0numbers the graph read from it
0cells of the map it votes in
93citing 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.

NCT05054257 phase1recruitingnot on this mapstarted 2021, after this paper: background citation

Safety and Efficacy of Anti-CD19 Chimeric Antigen Receptor-modified Autologous T Cells (CART19) in Patients with Relapsed/refractory CD19+ Acute Lymphoblastic Leukemia and Non-Hodgkin's Lymphoma. a Dose Escalation, Open-label, Phase I Study.

TypeinterventionalSponsorInstitute of Hematology and Blood Transfusion, Czech RepublicRan2021 to 2025Enrolled10ConditionsRelapsed or Refractory B-cell Acute Lymphoblastic Leukemia, Non-Hodgkin's Lymphoma Refractory, Non-Hodgkin's Lymphoma, RelapsedArmsAutologous CAR19 T lymphocytes
3 · Its place in the literature

Who cites it

93 citing papers in PubMed.

  1. Review
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  18. Review
  19. Article
  20. CAR T-Cell Production Using Nonviral Approaches.Journal of immunology research · 2021
    Review

33 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

14 authors.

Harjeet SinghDivision of Pediatrics, Children's Cancer Hospital, The University of Texas MD Anderson Cancer Center, Houston, Texas, United States of America.
Matthew J Figliola
Margaret J Dawson
Simon Olivares
Ling Zhang
Ge Yang
Sourindra Maiti
Pallavi Manuri
Vladimir Senyukov
Bipulendu Jena
Partow Kebriaei
Richard E Champlin
Helen Huls
Laurence J N Cooper

Funding

Tumor Evolution and Metastasis ProgramP30CA016672 · NCI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI Scott Kopetz · 1985 to 2026
$290.8M
PR1-specific CB T cells for Patients with Myeloid MalignanciesP01CA148600 · NCI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI KAUR, INDRESHPAL · 2011 to 2022
$24.4M
IMAGING T CELLS BY POSITRON EMISSION TOMOGRAPHYR01CA163587 · NCI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI NAJJAR, AMER M · 2012 to 2016
$2.9M
Quantitative single-cell biomarkers of T-cells to optimize tumor immunotherapyR01CA174385 · NCI · UNIVERSITY OF HOUSTON · PI COOPER, LAURENCE J.N., VARADARAJAN, NAVIN · 2012 to 2015
$2.1M
Adoptive immunotherapy after umbilical cord blood transplantR01CA124782 · NCI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI COOPER, LAURENCE J.N. · 2007 to 2011
$2.0M
T-cell Therapy for B-lineage Acute Lymphoblastic LeukemiaR01CA141303 · NCI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI COOPER, LAURENCE J.N. · 2010 to 2014
$1.5M
Enhancing the efficacy of CD19-specific cord blood-derived T CellsR01CA120956 · NCI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI COOPER, LAURENCE J.N. · 2007 to 2011
$1.5M
UCB-DERIVED CD19-SPECIFIC T CELLS FOR UNIVERSAL TREATMENT OF B-CELL MALIGNANCYR33CA116127 · NCI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI COOPER, LAURENCE J.N. · 2010 to 2011
$1.4M
UCB-DERIVED CD19-SPECIFIC T CELLS FOR UNIVERSAL TREATMENT OF B-CELL MALIGNANCYR21CA116127 · NCI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI COOPER, LAURENCE J.N. · 2007 to 2008
$371k
NCI NIH HHS CA16672NCI NIH HHS P01 CA148600NCI NIH HHS P30 CA016672NCI NIH HHS R01 CA120956NCI NIH HHS R01 CA124782NCI NIH HHS R01 CA141303NCI NIH HHS R01 CA163587NCI NIH HHS R01 CA174385NCI NIH HHS R21 CA116127NCI NIH HHS R33 CA116127
6 · The paper itself

Abstract

Adoptive transfer of T cells expressing a CD19-specific chimeric antigen receptor (CAR) is being evaluated in multiple clinical trials. Our current approach to adoptive immunotherapy is based on a second generation CAR (designated CD19RCD28) that signals through a CD28 and CD3-ζ endodomain. T cells are electroporated with DNA plasmids from the Sleeping Beauty (SB) transposon/transposase system to express this CAR. Stable integrants of genetically modified T cells can then be retrieved when co-cultured with designer artificial antigen presenting cells (aAPC) in the presence of interleukin (IL)-2 and 21. Here, we reveal how the platform technologies of SB-mediated transposition and CAR-dependent propagation on aAPC were adapted for human application. Indeed, we have initiated clinical trials in patients with high-risk B-lineage malignancies undergoing autologous and allogeneic hematopoietic stem-cell transplantation (HSCT). We describe the process to manufacture clinical grade CD19-specific T cells derived from healthy donors. Three validation runs were completed in compliance with current good manufacturing practice for Phase I/II trials demonstrating that by 28 days of co-culture on γ-irradiated aAPC ∼10(10) T cells were produced of which >95% expressed CAR. These genetically modified and propagated T cells met all quality control testing and release criteria in support of infusion.

Indexed as

Antigen-Presenting CellsAntigens, CD19CD28 AntigensCD3 ComplexCell ProliferationClinical Trials as TopicCoculture TechniquesDNA Transposable ElementsElectroporationGene ExpressionGenetic TherapyGene Transfer TechniquesHematopoietic Stem Cell TransplantationHumansImmunotherapy, AdoptiveInterleukin-2Antigens, CD19CD28 AntigensCD3 antigen, zeta chainCD3 ComplexDNA Transposable ElementsInterleukin-2Mutant Chimeric ProteinsTransposases

Identifiers

PMID23741305
PMCPMC3669363

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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.