Evidence map›Paper›PMID 40579924›Full record

ArticleNeuro-oncology2025

Mesothelin is a surface antigen present on human meningioma and can be effectively targeted by CAR T-cells.

Rishab Ramapriyan, Fred G Barker, Leland G Richardson, Jing Sun, Gust Vandecandelaere, Jane M Shim, Guillaume De Vlaminck, Matthew Gaffey, Eric P Grewal, Masih Tazhibi and 24 more

Abstract read
PubMed Full text at PMC Publisher
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Article in Neuro-oncology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

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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

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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

3 citing papers in PubMed.

  1. Review
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4 · The record

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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

34 authors.

Rishab RamapriyanDepartment of Neurosurgery, Mass General Brigham and Harvard Medical School, Boston, Massachusetts, USA.
Fred G BarkerDepartment of Neurosurgery, Mass General Brigham and Harvard Medical School, Boston, Massachusetts, USA.
Leland G RichardsonDepartment of Neurosurgery, Mass General Brigham and Harvard Medical School, Boston, Massachusetts, USA.
Jing SunDepartment of Neurosurgery, Mass General Brigham and Harvard Medical School, Boston, Massachusetts, USA.
Gust VandecandelaereDepartment of Neurosurgery, Mass General Brigham and Harvard Medical School, Boston, Massachusetts, USA.
Jane M ShimDepartment of Neurosurgery, Mass General Brigham and Harvard Medical School, Boston, Massachusetts, USA.
Guillaume De VlaminckDepartment of Neurosurgery, Mass General Brigham and Harvard Medical School, Boston, Massachusetts, USA.
Matthew GaffeyDepartment of Neurosurgery, Mass General Brigham and Harvard Medical School, Boston, Massachusetts, USA.
Eric P GrewalDepartment of Pathology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA.
Masih TazhibiDepartment of Neurosurgery, Mass General Brigham and Harvard Medical School, Boston, Massachusetts, USA.
Kourosh MorshedyMass General Cancer Center, Krantz Family Center for Cancer Research, Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA.
Amir R ArefDivision of Gastrointestinal and Oncologic Surgery, Department of Surgery, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA.
Syeda M BatoolDepartment of Neurosurgery, Mass General Brigham and Harvard Medical School, Boston, Massachusetts, USA.
Xiaopeng GuoDepartment of Neurosurgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
Nazanin IjadMass General Cancer Center, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA.
Leonora BalajDepartment of Neurosurgery, Mass General Brigham and Harvard Medical School, Boston, Massachusetts, USA.ORCID 0000-0003-0931-9715
Hiroaki WakimotoDepartment of Neurosurgery, Mass General Brigham and Harvard Medical School, Boston, Massachusetts, USA.ORCID 0000-0001-8225-241X
Maria Martinez-Lage
Matthew J FrigaultCellular Immunotherapy Program, Mass General Cancer Center, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA.
Mark B LeickCellular Immunotherapy Program, Mass General Cancer Center, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA.
Joshua D BernstockDepartment of Neurosurgery, Mass General Brigham and Harvard Medical School, Boston, Massachusetts, USA.ORCID 0000-0002-7814-3867
Wenya Linda BiDepartment of Neurosurgery, Mass General Brigham and Harvard Medical School, Boston, Massachusetts, USA.
Bob S CarterDepartment of Neurosurgery, Mass General Brigham and Harvard Medical School, Boston, Massachusetts, USA.
E Antonio ChioccaDepartment of Neurosurgery, Mass General Brigham and Harvard Medical School, Boston, Massachusetts, USA.
Jorg DietrichDepartment of Neurology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA.ORCID 0000-0001-8291-0136
Elizabeth R GerstnerDepartment of Neurology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA.
Genevieve M BolandDivision of Gastrointestinal and Oncologic Surgery, Department of Surgery, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA.
Brian V NahedDepartment of Neurosurgery, Mass General Brigham and Harvard Medical School, Boston, Massachusetts, USA.
Scott R PlotkinDepartment of Neurology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA.
Russell W JenkinsBroad Institute of MIT and Harvard, Cambridge, MA, USA.
Priscilla K BrastianosDepartment of Neurology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA.
William T CurryDepartment of Neurosurgery, Mass General Brigham and Harvard Medical School, Boston, Massachusetts, USA.
Marcela V MausCellular Immunotherapy Program, Mass General Cancer Center, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA.ORCID 0000-0002-7578-0393
Bryan D ChoiDepartment of Neurosurgery, Mass General Brigham and Harvard Medical School, Boston, Massachusetts, USA.ORCID 0000-0002-5090-2470

Funding

A Shot for LifeEdward S. Toole Glioblastoma Research FundNational Brain Tumor SocietyNeurosurgery Research and Education Foundation NIH R01CA294071Swim Across AmericaThe Jenny Fund in honor of Jen GureckisWilliam G. Markos Fund for Brain Tumor Immunotherapy
6 · The paper itself

Abstract

backgroundMeningioma is the most common primary CNS tumor, with high-grade cases exhibiting aggressive behavior, frequent recurrence, and poor prognosis. Currently, no systemic therapies are approved for recurrent or malignant meningiomas. Chimeric antigen receptor (CAR) T-cell therapy has shown efficacy in hematologic malignancies and promise for solid tumors, but its use for meningiomas has been underexplored. Mesothelin, a glycoprotein overexpressed in several solid tumors of mesodermal origin, may serve as a viable immunotherapeutic target. This study aimed to evaluate mesothelin as a CAR T-cell target in meningiomas.

methodsMesothelin expression was analyzed in patient-derived meningioma samples using immunohistochemistry, flow cytometry, and droplet digital PCR. Mesothelin-specific CAR T-cells were generated and evaluated invitro, exvivo using patient-derived organotypic tumor spheroids (PDOTS), and invivo using orthotopic meningioma mouse models of human xenografts. Cytotoxicity, T-cell proliferation, cytokine secretion, and tumor clearance were assessed.

resultsMesothelin was detected in a subset of tumors across all meningioma grades at the transcript and protein levels, with surface expression confirmed in patient-derived primary cells. Mesothelin-specific CAR T-cells exhibited potent and specific cytotoxicity, T-cell activation, and cytokine secretion in vitro and effectively eliminated PDOTS. In orthotopic human xenograft models, mesothelin CAR T-cell therapy led to significant tumor regression and prolonged survival.

conclusionsMesothelin is a viable CAR T-cell target for meningiomas, and mesothelin-specific CAR T-cell therapy shows strong preclinical efficacy. These findings provide a rationale for early-phase clinical trials of mesothelin CAR T-cell therapy in patients with refractory meningiomas.

Indexed as

GPI-Linked ProteinsImmunotherapy, AdoptiveMeningeal NeoplasmsMeningiomaReceptors, Chimeric AntigenT-LymphocytesAnimalsFemaleHumansMaleMesothelinMicePrognosisTumor Cells, CulturedXenograft Model Antitumor AssaysGPI-Linked ProteinsMesothelinReceptors, Chimeric Antigenbrain neoplasmsCAR T-Cell therapyimmunotherapymeningiomamesothelin

Identifiers

PMID40579924
PMCPMC12916738

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