Locoregional delivery of IL-13Rα2-targeting CAR-T cells in recurrent high-grade glioma: a phase 1 trial.
Journal
Nature medicine
ISSN: 1546-170X
Titre abrégé: Nat Med
Pays: United States
ID NLM: 9502015
Informations de publication
Date de publication:
Apr 2024
Apr 2024
Historique:
received:
27
06
2023
accepted:
15
02
2024
pubmed:
8
3
2024
medline:
8
3
2024
entrez:
7
3
2024
Statut:
ppublish
Résumé
Chimeric antigen receptor T cell (CAR-T) therapy is an emerging strategy to improve treatment outcomes for recurrent high-grade glioma, a cancer that responds poorly to current therapies. Here we report a completed phase I trial evaluating IL-13Rα2-targeted CAR-T cells in 65 patients with recurrent high-grade glioma, the majority being recurrent glioblastoma (rGBM). Primary objectives were safety and feasibility, maximum tolerated dose/maximum feasible dose and a recommended phase 2 dose plan. Secondary objectives included overall survival, disease response, cytokine dynamics and tumor immune contexture biomarkers. This trial evolved to evaluate three routes of locoregional T cell administration (intratumoral (ICT), intraventricular (ICV) and dual ICT/ICV) and two manufacturing platforms, culminating in arm 5, which utilized dual ICT/ICV delivery and an optimized manufacturing process. Locoregional CAR-T cell administration was feasible and well tolerated, and as there were no dose-limiting toxicities across all arms, a maximum tolerated dose was not determined. Probable treatment-related grade 3+ toxicities were one grade 3 encephalopathy and one grade 3 ataxia. A clinical maximum feasible dose of 200 × 10
Identifiants
pubmed: 38454126
doi: 10.1038/s41591-024-02875-1
pii: 10.1038/s41591-024-02875-1
doi:
Banques de données
ClinicalTrials.gov
['NCT02208362']
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
1001-1012Subventions
Organisme : California Institute for Regenerative Medicine (CIRM)
ID : CLIN2-12153
Organisme : Gateway for Cancer Research (Gateway)
ID : G-14-600
Organisme : U.S. Department of Health & Human Services | U.S. Food and Drug Administration (U.S. Food & Drug Administration)
ID : R01FD005129
Organisme : U.S. Department of Health & Human Services | NIH | National Cancer Institute (NCI)
ID : K12CA001727
Organisme : U.S. Department of Health & Human Services | NIH | National Cancer Institute (NCI)
ID : R01CA155769
Commentaires et corrections
Type : ErratumIn
Informations de copyright
© 2024. The Author(s).
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