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

Authors

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, Kourosh Morshedy, Amir R Aref, Syeda M Batool, Xiaopeng Guo, Nazanin Ijad, Leonora Balaj, Hiroaki Wakimoto, Maria Martinez-Lage, Matthew J Frigault, Mark B Leick, Joshua D Bernstock, Wenya Linda Bi, Bob S Carter, E Antonio Chiocca, Jorg Dietrich, Elizabeth R Gerstner, Genevieve M Boland, Brian V Nahed, Scott R Plotkin, Russell W Jenkins, Priscilla K Brastianos, William T Curry, Marcela V Maus, Bryan D Choi

Published in

Neuro-oncology. Volume 27. Issue 12. Pages 3104-3118. Dec 01, 2025.

Abstract

Meningioma 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.
Mesothelin 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.
Mesothelin 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.
Mesothelin 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.

PMID:
40579924
Bibliographic data and abstract were imported from PubMed on 15 Sep 2026.

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