Evidence map›Paper›PMID 39086131›Full record

ArticleMolecular therapy : the journal of the American Society of Gene Therapy2024

Armored bicistronic CAR T cells with dominant-negative TGF-β receptor II to overcome resistance in glioblastoma.

Nannan Li, Jesse L Rodriguez, Yibo Yin, Meghan T Logun, Logan Zhang, Shengkun Yu, Kelly A Hicks, Jiasi Vicky Zhang, Laura Zhang, Chuncheng Xie and 7 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Molecular therapy : the journal of the American Society of Gene Therapy, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 50 papers.

0numbers the graph read from it
0cells of the map it votes in
50citing 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

50 citing papers in PubMed.

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  5. Engineering the next generation of cellular therapies for solid tumors: multi-specific armored CARs and TME reprogramming strategies.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2026
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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

17 authors.

Nannan LiDepartment of Neurosurgery, First Affiliated Hospital of Harbin Medical University, Harbin 150001, China; Glioblastoma Translational Center of Excellence, Abramson Cancer Center, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104, USA; Department of Neurosurgery, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104, USA; Center for Cellular Immunotherapies, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104, USA.
Jesse L RodriguezGlioblastoma Translational Center of Excellence, Abramson Cancer Center, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104, USA; Department of Neurosurgery, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104, USA; Center for Cellular Immunotherapies, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104, USA.
Yibo YinDepartment of Neurosurgery, First Affiliated Hospital of Harbin Medical University, Harbin 150001, China; Glioblastoma Translational Center of Excellence, Abramson Cancer Center, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104, USA; Department of Neurosurgery, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104, USA; Center for Cellular Immunotherapies, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104, USA.
Meghan T LogunGlioblastoma Translational Center of Excellence, Abramson Cancer Center, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104, USA; Department of Neurosurgery, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104, USA; Center for Cellular Immunotherapies, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104, USA.
Logan ZhangGlioblastoma Translational Center of Excellence, Abramson Cancer Center, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104, USA; Department of Neurosurgery, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104, USA; Center for Cellular Immunotherapies, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104, USA.
Shengkun YuDepartment of Neurosurgery, The Fourth Affiliated Hospital of Nanjing Medical University, Nanjing 211800, China.
Kelly A HicksGlioblastoma Translational Center of Excellence, Abramson Cancer Center, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104, USA; Department of Neurosurgery, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104, USA; Center for Cellular Immunotherapies, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104, USA.
Jiasi Vicky ZhangGlioblastoma Translational Center of Excellence, Abramson Cancer Center, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104, USA; Department of Neurosurgery, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104, USA; Center for Cellular Immunotherapies, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104, USA.
Laura ZhangGlioblastoma Translational Center of Excellence, Abramson Cancer Center, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104, USA; Department of Neurosurgery, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104, USA; Center for Cellular Immunotherapies, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104, USA.
Chuncheng XieDepartment of Neurosurgery, First Affiliated Hospital of Harbin Medical University, Harbin 150001, China.
Jiabin WangDepartment of Neurosurgery, First Affiliated Hospital of Harbin Medical University, Harbin 150001, China.
Tianyu WangDepartment of Neurosurgery, First Affiliated Hospital of Harbin Medical University, Harbin 150001, China.
Jiayi XuDepartment of Neurosurgery, First Affiliated Hospital of Harbin Medical University, Harbin 150001, China.
Joseph A FraiettaCenter for Cellular Immunotherapies, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104, USA.
Zev A BinderGlioblastoma Translational Center of Excellence, Abramson Cancer Center, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104, USA; Department of Neurosurgery, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104, USA; Center for Cellular Immunotherapies, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104, USA.
Zhiguo LinDepartment of Neurosurgery, First Affiliated Hospital of Harbin Medical University, Harbin 150001, China. Electronic address: linzhiguo@hotmail.com.
Donald M O'RourkeGlioblastoma Translational Center of Excellence, Abramson Cancer Center, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104, USA; Department of Neurosurgery, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104, USA; Center for Cellular Immunotherapies, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104, USA. Electronic address: donald.orourke@pennmedicine.upenn.edu.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Chimeric antigen receptor (CAR) T cells have shown significant efficacy in hematological diseases. However, CAR T therapy has demonstrated limited efficacy in solid tumors, including glioblastoma (GBM). One of the most important reasons is the immunosuppressive tumor microenvironment (TME), which promotes tumor growth and suppresses immune cells used to eliminate tumor cells. The human transforming growth factor β (TGF-β) plays a crucial role in forming the suppressive GBM TME and driving the suppression of the anti-GBM response. To mitigate TGF-β-mediated suppressive activity, we combined a dominant-negative TGF-β receptor II (dnTGFβRII) with our previous bicistronic CART-EGFR-IL13Rα2 construct, currently being evaluated in a clinical trial, to generate CART-EGFR-IL13Rα2-dnTGFβRII, a tri-modular construct we are developing for clinical application. We hypothesized that this approach would more effectively subvert resistance mechanisms observed with GBM. Our data suggest that CART-EGFR-IL13Rα2-dnTGFβRII significantly augments T cell proliferation, enhances functional responses, and improves the fitness of bystander cells, particularly by decreasing the TGF-β concentration in a TGF-β-rich TME. In addition, in vivo studies validate the safety and efficacy of the dnTGFβRII cooperating with CARs in targeting and eradicating GBM in an NSG mouse model.

Indexed as

GlioblastomaImmunotherapy, AdoptiveReceptors, Chimeric AntigenReceptor, Transforming Growth Factor-beta Type IIAnimalsCell Line, TumorDisease Models, AnimalDrug Resistance, NeoplasmErbB ReceptorsHumansInterleukin-13 Receptor alpha2 SubunitMiceT-LymphocytesTransforming Growth Factor betaTumor MicroenvironmentXenograft Model Antitumor AssaysErbB ReceptorsInterleukin-13 Receptor alpha2 SubunitReceptors, Chimeric AntigenReceptor, Transforming Growth Factor-beta Type IITGFBR2 protein, humanTransforming Growth Factor betaantigenic heterogeneityCAR-TGBMimmunosuppressive TMETGF-β

Identifiers

PMID39086131
PMCPMC11489531

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.