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We have previously shown that the disialoganglioside GD2 is highly expressed on H3K27M-mutated glioma cells and have demonstrated promising preclinical efficacy of GD2-directed chimeric antigen receptor (CAR) T cells\n                    <jats:sup>2<\/jats:sup>\n                    , providing the rationale for a first-in-human phase I clinical trial (NCT04196413). Because CAR T cell-induced brainstem inflammation can result in obstructive hydrocephalus, increased intracranial pressure and dangerous tissue shifts, neurocritical care precautions were incorporated. Here we present the clinical experience from the first four patients with H3K27M-mutated DIPG or spinal cord\u00a0DMG treated with GD2-CAR T cells at dose level 1 (1\u2009\u00d7\u200910\n                    <jats:sup>6<\/jats:sup>\n                    GD2-CAR T cells per kg administered intravenously). Patients who exhibited clinical benefit were eligible for subsequent GD2-CAR T cell infusions administered intracerebroventricularly\n                    <jats:sup>3<\/jats:sup>\n                    . Toxicity was largely related to the location of the tumour and was reversible with intensive supportive care. On-target, off-tumour toxicity was not observed. Three of four patients exhibited clinical and radiographic improvement. Pro-inflammatory cytokine levels were increased in the plasma and cerebrospinal fluid. Transcriptomic analyses of 65,598 single cells from CAR T cell products and cerebrospinal fluid elucidate heterogeneity in response between participants and administration routes. These early results underscore the promise of this therapeutic\u00a0approach for patients with\u00a0H3K27M-mutated DIPG or spinal cord\u00a0DMG.\n                  <\/jats:p>","DOI":"10.1038\/s41586-022-04489-4","type":"journal-article","created":{"date-parts":[[2022,2,7]],"date-time":"2022-02-07T12:03:14Z","timestamp":1644235394000},"page":"934-941","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":841,"title":["GD2-CAR T cell therapy for H3K27M-mutated diffuse midline gliomas"],"prefix":"10.1038","volume":"603","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6969-8011","authenticated-orcid":false,"given":"Robbie 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C.L.M. is a cofounder and holds equity in Lyell Immunopharma and Syncopation Life Sciences, which are developing CAR-based therapies, Red Tree Venture Capital, Ensme and Mammoth and consults for Lyell, Syncopation, Red Tree, NeoImmune Tech, Apricity, Nektar, Immatics, Ensoma and Mammoth. R.G.M. is a cofounder of and holds equity in Syncopation Life Sciences; he is also a consultant for Lyell Immunopharma, Syncopation Life Sciences, NKarta, Gamma Delta Therapeutics, Aptorum Group, Illumina Radiopharmaceuticals, ImmunAI,\u00a0Arovella Therapeutics and Zai Lab. M.M. is on the scientific advisory board for Cygnal Therapeutics.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}]}}