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• W4384400585 abstract "ABSTRACT The non-clinical assessment of CAR-T cells demands innovative models that are capable of predicting safety and efficacy in the clinical setting. Here, we present a novel solid tumor-on-chip model that allows CAR-T cell perfusion and integrates the vasculature and tumor lesions to recapitulate key events of CAR-T cell performance including extravasation, tumor infiltration and cytokine release. We assessed CAR-T cells targeting the ROR1 antigen against tumor aggregates that were derived from a breast cancer cell line and primary breast cancer organoids. The data show the temporal kinetic of ROR1 CAR-T cell migration and expansion, lytic activity and cytokine production over the course of 8 days, and reveal a correlation between anti-tumor efficacy and ROR1 antigen density on tumor cells. CAR-modified T cells extravasated faster, infiltrated tumor lesions stronger, persisted longer and in higher numbers than non-CAR modified T cells. Intriguingly, we detected cytokine release levels and kinetics typically observed in patients who developed cytokine release syndrome, and administered dasatinib as a pharmacologic OFF switch to control this inflammatory response. The data illustrate the ability of this tumor-on-chip platform to assess parameters associated withherapeutic outcome and the potential to aid in patient stratification and monitoring of CAR-T cell therapy." @default.
• W4384400585 created "2023-07-16" @default.
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• W4384400585 date "2023-07-15" @default.
• W4384400585 modified "2023-10-03" @default.
• W4384400585 title "Solid tumor-on-chip model for efficacy and safety assessment of CAR-T cell therapy" @default.
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• W4384400585 doi "https://doi.org/10.1101/2023.07.13.548856" @default.
• W4384400585 hasPublicationYear "2023" @default.
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