Intracerebroventricular B7-H3-targeting CAR T cells for diffuse intrinsic pontine glioma: a phase 1 trial
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Le résumé fourni par la source
Abstract Diffuse intrinsic pontine glioma (DIPG) is a fatal central nervous system (CNS) tumor that confers a median survival of 11 months. As B7-H3 is expressed on pediatric CNS tumors, we conducted BrainChild-03, a single-center, dose-escalation phase 1 clinical trial of repetitive intracerebroventricular (ICV) dosing of B7-H3-targeting chimeric antigen receptor T cells (B7-H3 CAR T cells) for children with recurrent or refractory CNS tumors and DIPG. Here we report results from Arm C, restricted to patients with DIPG. The primary objectives were to assess feasibility and tolerability, which were both met. Secondary objectives included assessments of CAR T cell distribution and survival. A total of 23 patients with DIPG enrolled, and 21 were treated with repeated doses of ICV B7-H3 CAR T cells using intra-patient dose-escalation regimens without previous lymphodepletion. Concurrent tumor-directed therapy, including re-irradiation, was not allowed while on protocol therapy. We delivered a total of 253 ICV doses and established the highest planned dose regimen, DR4, which escalated up to 10 × 10 7 cells per dose, as the maximally tolerated dose regimen. Common adverse events included headache, fatigue and fever. There was one dose-limiting toxicity (intratumoral hemorrhage) during DR2. For all treated patients ( n = 21), the median survival from their initial CAR T cell infusion was 10.7 months and the median survival from diagnosis was 19.8 months with 3 patients still alive at 44, 45 and 52 months from diagnosis. Ultimately, this completed first-in-human trial shows that repetitive ICV dosing of B7-H3 CAR T cells in pediatric and young adult patients with DIPG is tolerable, including multiyear repeated dosing, and may have clinical efficacy that warrants further investigation on a multisite phase 2 trial. ClinicalTrials.gov registration: NCT04185038 .
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Le contrôle bibliographique ouvert
DOI retrouvé dans Crossref DOI retrouvé ; titre concordant.
- Titre Crossref
- Intracerebroventricular B7-H3-targeting CAR T cells for diffuse intrinsic pontine glioma: a phase 1 trial
- Date Crossref
- 07/01/2025
- Éditeur
- Springer Science and Business Media LLC
- Type
- journal-article
Ce recoupement confirme des métadonnées liées au DOI. Il ne confirme ni la méthode ni les conclusions de l’étude, et il ne compte pas comme une seconde source scientifique indépendante.
Où se fait cette recherche
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Seattle Children's Hospital Department of Radiology pays non établi dans la noticeÉtablissement de santé
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University of Washington Department of Pediatrics pays non établi dans la noticeUniversité ou école supérieure
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Seattle Children's Research Institute Ben Towne Center for Childhood Cancer and Blood Disorders Research pays non établi dans la noticeÉtablissement de santé
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Neurological Surgery pays non établi dans la noticeÉtablissement de santé
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Centro de Investigación Médica Aplicada pays non établi dans la noticeOrganisation à but non lucratif
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Universidad de Navarra pays non établi dans la noticeUniversité ou école supérieure
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Hunter Medical Research Institute Precision Medicine Research Program pays non établi dans la noticeStructure de recherche
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University of Newcastle Australia pays non établi dans la noticeUniversité ou école supérieure
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Children's Hospital of Philadelphia Division of Oncology pays non établi dans la noticeOrganisme public
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University of Pennsylvania Department of Pediatrics pays non établi dans la noticeUniversité ou école supérieure
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Seattle Children's Therapeutics pays non établi dans la noticeInstitution
Department of Radiology — Seattle Children's Hospital, Department of Pediatrics — University of Washington et Ben Towne Center for Childhood Cancer and Blood Disorders Research — Seattle Children's Research Institute, avec 9 autres affiliations.
Une affiliation ne permet pas de déduire la nationalité d’un auteur.