Evidence map›Paper›PMID 38982561›Full record

ArticleNeuro-oncology2024

IL-13Rα2/TGF-β bispecific CAR-T cells counter TGF-β-mediated immune suppression and potentiate anti-tumor responses in glioblastoma.

Andrew J Hou, Ryan M Shih, Benjamin R Uy, Amanda Shafer, ZeNan L Chang, Begonya Comin-Anduix, Miriam Guemes, Zoran Galic, Su Phyu, Hideho Okada and 6 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Neuro-oncology, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 54 papers.

0numbers the graph read from it
0cells of the map it votes in
54citing 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

54 citing papers in PubMed.

  1. Review
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  7. Programming T cells for intercellular genome editing.bioRxiv : the preprint server for biology · 2026
    Article
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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

16 authors.

Andrew J HouDepartment of Chemical and Biomolecular Engineering, University of California, Los Angeles, California, USA.
Ryan M ShihDepartment of Molecular Biology, University of California, Los Angeles, California, USA.ORCID 0000-0002-3570-867X
Benjamin R UyDepartment of Neurosurgery, University of California, Los Angeles, California, USA.
Amanda ShaferDepartment of Microbiology, Immunology, and Molecular Genetics, University of California, Los Angeles, California, USA.
ZeNan L ChangDepartment of Molecular Biology, University of California, Los Angeles, California, USA.
Begonya Comin-AnduixDepartment of Surgery, University of California, Los Angeles, California, USA.
Miriam GuemesDepartment of Medicine, Division of Hematology/Oncology, University of California, Los Angeles, California, USA.
Zoran GalicJonsson Comprehensive Cancer Center, University of California, Los Angeles, California, USA.
Su PhyuDepartment of Neurosurgery, University of California, San Francisco, California, USA.
Hideho OkadaDepartment of Neurosurgery, University of California, San Francisco, California, USA.ORCID 0000-0003-0076-9920
Katie B GrausamBoard of Governor's Regenerative Medicine Institute, Cedars-Sinai Medical Center, Los Angeles, California, USA.
Joshua J BreunigBoard of Governor's Regenerative Medicine Institute, Cedars-Sinai Medical Center, Los Angeles, California, USA.
Christine E BrownDepartment of Hematology & Hematopoietic Cell Transplantation, City of Hope National Medical Center and Beckman Research Institute, Duarte, California, USA.
David A NathansonJonsson Comprehensive Cancer Center, University of California, Los Angeles, California, USA.
Robert M PrinsDepartment of Neurosurgery, University of California, Los Angeles, California, USA.ORCID 0000-0002-6282-6583
Yvonne Y ChenDepartment of Chemical and Biomolecular Engineering, University of California, Los Angeles, California, USA.ORCID 0000-0002-5583-119X

Funding

Women's CancersP30CA016042 · NCI · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI Samuel Wheeler French · 1985 to 2026
$134.5M
UCLA-Caltech Medical Scientist Training ProgramT32GM008042 · NIGMS · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI AJIJOLA, OLUJIMI A, DAWSON, DAVID WAYNE · 1985 to 2023
$29.9M
UCLA SPORE in Brain CancerP50CA211015 · NCI · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI David A. Nathanson · 2017 to 2026
$25.2M
TUMOR CELL SURFACES AND CHROMOSOMEST32CA009056 · NCI · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI Gay M Crooks, David A. Nathanson · 1985 to 2026
$10.5M
Preclinical development of breakthrough immunotherapy for brain tumorsR35NS105068 · NINDS · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI OKADA, HIDEHO · 2018 to 2025
$6.0M
UCLA-Caltech Medical Scientist Training ProgramT32GM152342 · NIGMS · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI Olujimi A Ajijola, David Wayne Dawson · 2024 to 2026
$5.3M
Programming multi-pronged immune response to glioblastoma with IL-13Ra2/TGF-b CAR-T cell therapy.R01NS126849 · NINDS · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI Yvonne Yu-Hsuan Chen · 2023 to 2026
$2.4M
Jean and Stephen KaplanMark Foundation for Cancer Research 18-029-ELANCI NIH HHS P30 CA016042NCI NIH HHS P50 CA211015NCI NIH HHS T32 CA009056NIGMS NIH HHS T32 GM008042NIGMS NIH HHS T32 GM152342NINDS NIH HHS 1R01NS126849NINDS NIH HHS R01 NS126849NINDS NIH HHS R35 NS105068The National Cancer Institute P50CA211015UCLA Jonsson Comprehensive Cancer Center #T32 CA009056
6 · The paper itself

Abstract

backgroundChimeric antigen receptor (CAR)-T cell therapies targeting glioblastoma (GBM)-associated antigens such as interleukin-13 receptor subunit alpha-2 (IL-13Rα2) have achieved limited clinical efficacy to date, in part due to an immunosuppressive tumor microenvironment (TME) characterized by inhibitory molecules such as transforming growth factor-beta (TGF-β). The aim of this study was to engineer more potent GBM-targeting CAR-T cells by countering TGF-β-mediated immune suppression in the TME.

methodsWe engineered a single-chain, bispecific CAR targeting IL-13Rα2 and TGF-β, which programs tumor-specific T cells to convert TGF-β from an immunosuppressant to an immunostimulant. Bispecific IL-13Rα2/TGF-β CAR-T cells were evaluated for efficacy and safety against both patient-derived GBM xenografts and syngeneic models of murine glioma.

resultsTreatment with IL-13Rα2/TGF-β CAR-T cells leads to greater T-cell infiltration and reduced suppressive myeloid cell presence in the tumor-bearing brain compared to treatment with conventional IL-13Rα2 CAR-T cells, resulting in improved survival in both patient-derived GBM xenografts and syngeneic models of murine glioma.

conclusionsOur findings demonstrate that by reprogramming tumor-specific T-cell responses to TGF-β, bispecific IL-13Rα2/TGF-β CAR-T cells resist and remodel the immunosuppressive TME to drive potent anti-tumor responses in GBM.

Indexed as

Brain NeoplasmsGlioblastomaImmunotherapy, AdoptiveInterleukin-13 Receptor alpha2 SubunitReceptors, Chimeric AntigenTransforming Growth Factor betaTumor MicroenvironmentXenograft Model Antitumor AssaysAnimalsCell Line, TumorHumansMiceT-LymphocytesTumor Cells, CulturedIL13RA2 protein, humanInterleukin-13 Receptor alpha2 SubunitReceptors, Chimeric AntigenTransforming Growth Factor betaCAR-T cell therapyglioblastomaimmunotherapyTGF-βtumor microenvironment

Identifiers

PMID38982561
PMCPMC11449012

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.