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Mimicking CAR-T mediated CRS on human endothelium using microphysiological systems

Weener, H.J. (2020) Mimicking CAR-T mediated CRS on human endothelium using microphysiological systems.

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Abstract:Chimeric antigen receptor T cell (CAR-T cell) immunotherapy is a novel therapy that has been approved in Europe and the United States against haematological malignancies. Current therapies have CAR-T cells release significant amounts of cytokines that help in the breakdown of the tumour, but also have adverse effects known as a cytokine release syndrome. The CAR-T cells release too many cytokines, destroying surrounding tissues and hospitalizing the patients. The endothelium is broken down by these cytokines, further enhancing their release. Current disease models lack in mimicking this interaction between cytokines and endothelium, so in this study a microphysiological blood vessel-on-chip is used to mimic the interaction that takes place in vivo. This system is seeded with human embryonic stem cell derived endothelial cells that are cultured in a circular collagen channel. After 72 hours of culturing, the endothelial cells had formed a monolayer. Cytokines harvested from CAR-T cells co-cultured with tumour cells were then applied for 24 hours. Their effect was measured using fluorescent angiography and immunostainings for DNA, VE-cadherin, ICAM-1, and actin. The results show that there is a decrease in cell viability if the cytokine concentration in the media is increased, indicating that the effect of CAR-T cell derived cytokines on human endothelium can be mimicked in the proposed device.
Item Type:Essay (Master)
Faculty:TNW: Science and Technology
Subject:33 physics, 42 biology, 44 medicine
Programme:Biomedical Engineering MSc (66226)
Link to this item:http://purl.utwente.nl/essays/85451
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