Evidence map›Paper›PMID 23295945›Full record

ArticleMolecular therapy : the journal of the American Society of Gene Therapy2013

Bispecific T-cells expressing polyclonal repertoire of endogenous γδ T-cell receptors and introduced CD19-specific chimeric antigen receptor.

Drew C Deniger, Kirsten Switzer, Tiejuan Mi, Sourindra Maiti, Lenka Hurton, Harjeet Singh, Helen Huls, Simon Olivares, Dean A Lee, Richard E Champlin and 1 more

Registry-linked trialOpen access · hybridAbstract read
In one paragraph

Article in Molecular therapy : the journal of the American Society of Gene Therapy, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT04102436 (A Phase II Study Using the Administration of Autologous T-Cells Engineered Using the Sleeping Beauty Transposon/Transposase System to Express T-Cell Receptors Reactive Against Mutated Neoantigens in Patients With Metastatic Cancer), which is not on this map. Cited by 117 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
117citing papers in PubMed, 1 pooled it
6.3field-weighted citation impact, top 3% of its field
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.

NCT04102436 phase2withdrawnnot on this mapstarted 2024, after this paper: background citation

A Phase II Study Using the Administration of Autologous T-Cells Engineered Using the Sleeping Beauty Transposon/Transposase System to Express T-Cell Receptors Reactive Against Mutated Neoantigens in Patients With Metastatic Cancer

TypeinterventionalSponsorNational Cancer Institute (NCI)Ran2024 to 2024Enrolled0ConditionsEndocrine/Neuroendocrine, Non-Small Cell Lung Cancer, Breast Cancer, Gastrointestinal/Genitourinary CancersArmsFludarabine, Cyclophosphamide, Aldesleukin, Sleeping Beauty Transposed PBL
3 · Its place in the literature

Who cites it

117 citing papers in PubMed, 1 synthesis or guideline pooled it, 178 citations in OpenAlex.

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57 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

11 authors at 2 institutions in 1 country.

Drew C DenigerThe University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Kirsten Switzer
Tiejuan Mi
Sourindra Maiti
Lenka Hurton
Harjeet Singh
Helen Huls
Simon Olivares
Dean A Lee
Richard E Champlin
Laurence J N Cooper
The University of Texas MD Anderson Cancer Center · USUniversity of Houston · US

Funding

Tumor Evolution and Metastasis ProgramP30CA016672 · NCI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI Scott Kopetz · 1985 to 2026
$290.8M
University of Texas M.D. Anderson Cancer SPORE-LeukemiaP50CA100632 · NCI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI KONOPLEVA, MARINA Y · 2003 to 2023
$43.7M
U OF TEXAS HLTH SCI CTR HOUSTON CENTER FOR CLINICAL AND TRANSLATIONAL SCIENCESUL1RR024148 · NCRR · UNIVERSITY OF TEXAS HLTH SCI CTR HOUSTON · PI MCPHERSON, DAVID D · 2006 to 2010
$27.9M
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
Center for Clinical and Translational SciencesTL1RR024147 · NCRR · UNIVERSITY OF TEXAS HLTH SCI CTR HOUSTON · PI MCPHERSON, DAVID D · 2006 to 2011
$2.3M
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
UT M.D. Anderson Cancer Center Lymphoma SPOREP50CA136411 · NCI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI KWAK, LARRY W · 2009 to 2011
$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 CA100632NCI NIH HHS CA120956NCI NIH HHS CA124782NCI NIH HHS CA136411NCI NIH HHS CA141303NCI NIH HHS CA163587NCI NIH HHS CA16672NCI NIH HHS P01 CA148600NCI NIH HHS P30 CA016672NCI NIH HHS P50 CA100632NCI NIH HHS P50 CA136411NCI NIH HHS R01 CA120956NCI NIH HHS R01 CA124782NCI NIH HHS R01 CA141303NCI NIH HHS R01 CA163587NCI NIH HHS R21 CA116127NCI NIH HHS R33 CA116127NCRR NIH HHS S10 RR026916NCRR NIH HHS S10RR026916NCRR NIH HHS TL1 RR024147NCRR NIH HHS UL1 RR024148
6 · The paper itself

Abstract

Even though other γδ T-cell subsets exhibit antitumor activity, adoptive transfer of γδ Tcells is currently limited to one subset (expressing Vγ9Vδ2 T-cell receptor (TCR)) due to dependence on aminobisphosphonates as the only clinically appealing reagent for propagating γδ T cells. Therefore, we developed an approach to propagate polyclonal γδ T cells and rendered them bispecific through expression of a CD19-specific chimeric antigen receptor (CAR). Peripheral blood mononuclear cells (PBMC) were electroporated with Sleeping Beauty (SB) transposon and transposase to enforce expression of CAR in multiple γδ T-cell subsets. CAR(+)γδ T cells were expanded on CD19(+) artificial antigen-presenting cells (aAPC), which resulted in >10(9) CAR(+)γδ T cells from <10(6) total cells. Digital multiplex assay detected TCR mRNA coding for Vδ1, Vδ2, and Vδ3 with Vγ2, Vγ7, Vγ8, Vγ9, and Vγ10 alleles. Polyclonal CAR(+)γδ T cells were functional when TCRγδ and CAR were stimulated and displayed enhanced killing of CD19(+) tumor cell lines compared with CAR(neg)γδ T cells. CD19(+) leukemia xenografts in mice were reduced with CAR(+)γδ T cells compared with control mice. Since CAR, SB, and aAPC have been adapted for human application, clinical trials can now focus on the therapeutic potential of polyclonal γδ T cells.

Indexed as

AnimalsAntigen-Presenting CellsAntigens, CD19Cell Line, TumorElectroporationHumansImmunotherapy, AdoptiveLeukemiaLeukocytes, MononuclearLymphocyte ActivationMiceMice, KnockoutReceptors, Antigen, T-Cell, gamma-deltaT-LymphocytesTransposasesAntigens, CD19Receptors, Antigen, T-Cell, gamma-deltasleeping beauty transposase, humanTransposases

Identifiers

PMID23295945
PMCPMC3589159
OpenAlexW1972700907

What OpenQuestion holds

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Read underepoch 390

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.