Evidence map›Paper›PMID 27548616›Full record

ArticlePloS one2016

Redirecting Specificity of T cells Using the Sleeping Beauty System to Express Chimeric Antigen Receptors by Mix-and-Matching of VL and VH Domains Targeting CD123+ Tumors.

Radhika Thokala, Simon Olivares, Tiejuan Mi, Sourindra Maiti, Drew Deniger, Helen Huls, Hiroki Torikai, Harjeet Singh, Richard E Champlin, Tamara Laskowski and 2 more

Open access · goldAbstract read
In one paragraph

Article in PloS one, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
36citing papers in PubMed, 1 pooled it
3.8field-weighted citation impact, top 5% 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.

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

36 citing papers in PubMed, 1 synthesis or guideline pooled it, 60 citations in OpenAlex.

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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

12 authors at 3 institutions in 1 country.

Radhika ThokalaDivision of Pediatrics, The University of Texas MD Anderson Cancer Center, Houston, Texas, United States of America.ORCID http://orcid.org/0000-0002-4279-4115
Simon OlivaresDivision of Pediatrics, The University of Texas MD Anderson Cancer Center, Houston, Texas, United States of America.
Tiejuan MiDivision of Pediatrics, The University of Texas MD Anderson Cancer Center, Houston, Texas, United States of America.
Sourindra MaitiDivision of Pediatrics, The University of Texas MD Anderson Cancer Center, Houston, Texas, United States of America.
Drew DenigerDivision of Pediatrics, The University of Texas MD Anderson Cancer Center, Houston, Texas, United States of America.
Helen HulsIntrexon Corporation, Germantown, Maryland, United States of America.
Hiroki TorikaiDivision of Pediatrics, The University of Texas MD Anderson Cancer Center, Houston, Texas, United States of America.
Harjeet SinghDivision of Pediatrics, The University of Texas MD Anderson Cancer Center, Houston, Texas, United States of America.
Richard E ChamplinStem Cell Transplantation and Cellular Therapy, The University of Texas MD Anderson Cancer Center, Houston, Texas, United States of America.
Tamara LaskowskiDivision of Pediatrics, The University of Texas MD Anderson Cancer Center, Houston, Texas, United States of America.
George McNamaraDivision of Pediatrics, The University of Texas MD Anderson Cancer Center, Houston, Texas, United States of America.
Laurence J N CooperDivision of Pediatrics, The University of Texas MD Anderson Cancer Center, Houston, Texas, United States of America.
The University of Texas MD Anderson Cancer Center · USIntelligent Fusion Technology (United States) · USNational Institutes of Health · 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
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
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
NCI 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 CA141303
6 · The paper itself

Abstract

Adoptive immunotherapy infusing T cells with engineered specificity for CD19 expressed on B- cell malignancies is generating enthusiasm to extend this approach to other hematological malignancies, such as acute myelogenous leukemia (AML). CD123, or interleukin 3 receptor alpha, is overexpressed on most AML and some lymphoid malignancies, such as acute lymphocytic leukemia (ALL), and has been an effective target for T cells expressing chimeric antigen receptors (CARs). The prototypical CAR encodes a VH and VL from one monoclonal antibody (mAb), coupled to a transmembrane domain and one or more cytoplasmic signaling domains. Previous studies showed that treatment of an experimental AML model with CD123-specific CAR T cells was therapeutic, but at the cost of impaired myelopoiesis, highlighting the need for systems to define the antigen threshold for CAR recognition. Here, we show that CARs can be engineered using VH and VL chains derived from different CD123-specific mAbs to generate a panel of CAR+ T cells. While all CARs exhibited specificity to CD123, one VH and VL combination had reduced lysis of normal hematopoietic stem cells. This CAR's in vivo anti-tumor activity was similar whether signaling occurred via chimeric CD28 or CD137, prolonging survival in both AML and ALL models. Co-expression of inducible caspase 9 eliminated CAR+ T cells. These data help support the use of CD123-specific CARs for treatment of CD123+ hematologic malignancies.

Indexed as

AnimalsB-LymphocytesCaspase 9CD28 AntigensCytotoxicity, ImmunologicDisease Models, AnimalGene ExpressionGenetic EngineeringHematopoietic Stem CellsHumansImmunotherapy, AdoptiveInterleukin-3 Receptor alpha SubunitLeukemia, Myeloid, AcuteMiceMice, Inbred NODMice, SCIDCASP9 protein, humanCaspase 9CD28 AntigensInterleukin-3 Receptor alpha SubunitRecombinant Fusion ProteinsSingle-Domain AntibodiesTumor Necrosis Factor Receptor Superfamily, Member 9

Identifiers

PMID27548616
PMCPMC4993583
OpenAlexW2515130157

What OpenQuestion holds

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Registered trials

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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.