{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T20:07:49Z","timestamp":1792786069728,"version":"4.5.0"},"reference-count":42,"publisher":"Oxford University Press (OUP)","issue":"10","license":[{"start":{"date-parts":[[2025,5,24]],"date-time":"2025-05-24T00:00:00Z","timestamp":1748044800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000005","name":"Department of Defense","doi-asserted-by":"publisher","award":["W81XWH-21-1-0221"],"award-info":[{"award-number":["W81XWH-21-1-0221"]}],"id":[{"id":"10.13039\/100000005","id-type":"DOI","asserted-by":"publisher"}]},{"name":"National Institute of Health","award":["5 K08 CA263179"],"award-info":[{"award-number":["5 K08 CA263179"]}]},{"DOI":"10.13039\/100007445","name":"Matthew Larson Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100007445","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Liv Like a Unicorn"},{"name":"Greyson Saves Foundation"},{"name":"Kourtney Rose Foundation"},{"name":"October Saves"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,10,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Diffuse midline glioma (DMG) and high-grade glioma are devastating pediatric central nervous system tumors that remain incurable. Recent chimeric antigen receptor (CAR) T cell studies have shown proof of concept and early signs of efficacy against DMG targeting GD2. Prior work and ongoing clinical trials have focused on using viral vectors to create permanent CAR T cells. However, virally transduced GD2-directed CAR T cells have shown significant neurotoxicity in both preclinical models and human trials.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We evaluated transient CAR T cells targeting GD2 created with mRNA, assessing for efficacy and safety in cell line, organoid, and in vivo xenograft models with repetitive intratumoral dosing.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>We show that mRNA GD2-directed CAR T cells are active against both cell lines and organoid models of DMG and high-grade glioma in vitro. Cytotoxicity consistently abates over 9 days, highlighting the potential to avoid toxicity from persistent T cell activity. In both pontine and thalamic DMG xenograft models, repeated doses of mRNA GD2-directed CAR T cells were titrated down to maintain therapeutic effects without causing neurologic toxicity.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Our results demonstrate the utility of transient mRNA CAR T cells delivered intratumorally to provide effective tumor killing with a defined half-life, allowing for modulation of the dose and potential side effects. We anticipate this study will expand the use of CAR T cell therapy for DMG and other central nervous system tumors and non-malignant disorders, where concern for toxicity from permanently expressing CAR T cells may hinder development.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/neuonc\/noaf115","type":"journal-article","created":{"date-parts":[[2025,4,26]],"date-time":"2025-04-26T08:15:28Z","timestamp":1745655328000},"page":"2684-2696","source":"Crossref","is-referenced-by-count":22,"title":["Transient mRNA CAR T cells targeting GD2 provide dose-adjusted efficacy against diffuse midline glioma and high-grade glioma models"],"prefix":"10.1093","volume":"27","author":[{"given":"Jessica B","family":"Foster","sequence":"first","affiliation":[{"name":"Department of Pediatrics, Perelman School of Medicine, University of Pennsylvania , Philadelphia, PA ,","place":["USA"]},{"name":"Division of Oncology, Children\u2019s Hospital of Philadelphia , Philadelphia, PA 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Philadelphia, PA ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Valerie","family":"Baubet","sequence":"additional","affiliation":[{"name":"Center for Data Driven Discovery in Biomedicine, Children\u2019s Hospital of Philadelphia , Philadelphia, PA ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peeyush N","family":"Goel","sequence":"additional","affiliation":[{"name":"Center for Data Driven Discovery in Biomedicine, Children\u2019s Hospital of Philadelphia , Philadelphia, PA ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicholas A","family":"Vitanza","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Seattle Children\u2019s Hospital, University of Washington , Seattle, WA ,","place":["USA"]},{"name":"Ben Towne Center for Childhood Cancer and Blood Disorder Research, Seattle Children\u2019s Research Institute , Seattle, WA ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1951-9828","authenticated-orcid":false,"given":"Javad","family":"Nazarian","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, University Children\u2019s Hospital, University of Zurich , Zurich ,","place":["Switzerland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mateusz","family":"Koptyra","sequence":"additional","affiliation":[{"name":"Center for Data Driven Discovery in Biomedicine, Children\u2019s Hospital of Philadelphia , Philadelphia, PA ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Phillip B","family":"Storm","sequence":"additional","affiliation":[{"name":"Center for Data Driven Discovery in Biomedicine, Children\u2019s Hospital of Philadelphia , Philadelphia, PA ,","place":["USA"]},{"name":"Division of Neurosurgery, Children\u2019s Hospital of Philadelphia , Philadelphia, PA 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