{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T23:30:10Z","timestamp":1787009410253,"version":"build-2736575974"},"reference-count":62,"publisher":"Oxford University Press (OUP)","issue":"12","license":[{"start":{"date-parts":[[2025,6,28]],"date-time":"2025-06-28T00:00:00Z","timestamp":1751068800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"DOI":"10.13039\/100005351","name":"Neurosurgery Research and Education Foundation","doi-asserted-by":"publisher","award":["NIH R01CA294071"],"award-info":[{"award-number":["NIH R01CA294071"]}],"id":[{"id":"10.13039\/100005351","id-type":"DOI","asserted-by":"publisher"}]},{"name":"William G. Markos Fund for Brain Tumor Immunotherapy"},{"name":"Edward S. Toole Glioblastoma Research Fund"},{"name":"A Shot for Life"},{"DOI":"10.13039\/100001512","name":"National Brain Tumor Society","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100001512","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100016947","name":"Swim Across America","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100016947","id-type":"DOI","asserted-by":"publisher"}]},{"name":"The Jenny Fund in honor of Jen Gureckis"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,12,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>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.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>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.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>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.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>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.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/neuonc\/noaf155","type":"journal-article","created":{"date-parts":[[2025,6,26]],"date-time":"2025-06-26T07:55:18Z","timestamp":1750924518000},"page":"3104-3118","source":"Crossref","is-referenced-by-count":6,"title":["Mesothelin is a surface antigen present on human meningioma and can be effectively targeted by CAR T-cells"],"prefix":"10.1093","volume":"27","author":[{"given":"Rishab","family":"Ramapriyan","sequence":"first","affiliation":[{"name":"Department of Neurosurgery, Mass General Brigham and Harvard Medical School , Boston, Massachusetts ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"suffix":"2nd","given":"Fred G","family":"Barker","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Mass General Brigham and Harvard Medical School , Boston, Massachusetts ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leland G","family":"Richardson","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Mass General Brigham and Harvard Medical School , Boston, Massachusetts ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing","family":"Sun","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Mass General Brigham and Harvard Medical School , Boston, Massachusetts ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gust","family":"Vandecandelaere","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Mass General Brigham and Harvard Medical School , Boston, Massachusetts ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jane M","family":"Shim","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Mass General 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