Potency monitoring of CAR T cells

Wang, Dongrui; Yang, Xin; Xella, Agata; Stern, Lawrence A.; Brown, Christine E.

doi:10.1016/bs.mcb.2022.07.010

Cited by 1 publication

(1 citation statement)

References 26 publications

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“…2 . For flow-cytometry-based recursive killing assays, patient CAR-T cell products were cocultured with patient-derived glioma tumor cells, and absolute numbers of viable tumor cells and CAR-T cells were enumerated by staining for CD45 and CD19 to distinguish between target cells and CAR-T cells 57 . All samples were acquired on MACSQuant Analyzer 10 (Miltenyi Biotec) and analyzed with FlowJo software (v10.1, TreeStar) and GraphPad Prism Software (v9).…”

Section: Methodsmentioning

confidence: 99%

Locoregional delivery of IL-13Rα2-targeting CAR-T cells in recurrent high-grade glioma: a phase 1 trial

Brown,

Hibbard,

Alizadeh

et al. 2024

Nat Med

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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 × 106 CAR-T cells per infusion cycle was achieved for arm 5; however, other arms either did not test or achieve this dose due to manufacturing feasibility. A recommended phase 2 dose will be refined in future studies based on data from this trial. Stable disease or better was achieved in 50% (29/58) of patients, with two partial responses, one complete response and a second complete response after additional CAR-T cycles off protocol. For rGBM, median overall survival for all patients was 7.7 months and for arm 5 was 10.2 months. Central nervous system increases in inflammatory cytokines, including IFNγ, CXCL9 and CXCL10, were associated with CAR-T cell administration and bioactivity. Pretreatment intratumoral CD3 T cell levels were positively associated with survival. These findings demonstrate that locoregional IL-13Rα2-targeted CAR-T therapy is safe with promising clinical activity in a subset of patients. ClinicalTrials.gov Identifier: NCT02208362.

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Section: Methodsmentioning

confidence: 99%