Multi-antigen-targeting T cells in pediatric central nervous system tumors: a phase 1 trial
Mené sur 51 patients pédiatriques atteints d'une tumeur du système nerveux central, cet essai de phase I détermine la dose maximale tolérée d'une immunothérapie à base de cellules T ciblant WT1 et PRAME puis évalue son efficacité du point de vue de la survie globale et de la survie sans progression
Central nervous system (CNS) tumors are the deadliest cancers in children, highlighting the need for new therapies. The tumor-associated antigens (TAAs) WT1, PRAME and survivin are widely expressed by these tumors, and a manufacturing technique has been developed to target these intracellular TAAs using autologous, nongenetically engineered T cells. Here we therefore conducted ReMIND, an open-label, phase 1 adaptive dose-finding study to determine the safety/feasibility of autologous, systemically administered trivalent T cells targeting WT1, PRAME and survivin in children with CNS tumors. Eligible patients had newly diagnosed diffuse intrinsic pontine glioma without lymphodepletion (arm A, n = 16 enrolled, n = 11 infused) and relapsed/recurrent nonbrainstem CNS malignancies without (arm B, n = 28 enrolled, n = 18 infused) or with (arm C, n = 7 enrolled, n = 4 infused) lymphodepletion. Primary end points were safety, feasibility and maximum tolerated dose determination; secondary end points included preliminary efficacy and immunobiological correlates, including in vivo TAA-T persistence and systemic immune activation. Dose level 3 (8 × 107 cells per m2 per dose) was determined as the maximum tolerated dose. Treatment was well tolerated with fatigue and headache being the most common adverse events, although two possibly related serious adverse events of tumor swelling occurred. One grade 5 event in a patient with diffuse intrinsic pontine glioma with hydrocephalus, tumor edema and respiratory failure was categorized as a dose-limiting toxicity. Median overall survival for arm A was 13.7 months from diagnosis (range, 6.2–32.0) and median progression-free survival for arms B/C was 5.0 months from infusion (range, 0.5–51.6). Three patients in arms B/C are alive without disease at 31.8, 41.2 and 51.6 months without further treatment, including one complete response. This trial met safety/feasibility primary end points with some preliminary signals of efficacy. ClinicalTrials.gov registration: NCT03652545.
Nature Medicine , article en libre accès, 2026