This article and associated images are based on a poster originally authored by W. Strijker, I. Voskamp, B. Duggan, L. de Haan, W. Celus, and L. Gijzen and presented at ELRIG Drug Discovery 2025 in affiliation with MIMETAS BV and Montis Biosciences.
This poster is being hosted on this website in its raw form, without modifications. It has not undergone peer review but has been reviewed to meet AZoNetwork's editorial quality standards. The information contained is for informational purposes only and should not be considered validated by independent peer assessment.
Targeting the TME
The immunosuppressive tumor microenvironment (TME) has recently emerged as a novel therapeutic target. Improved preclinical tools offer enhanced mechanistic insights and support the development of targeted therapies.
We studied the role of perivascular macrophages (PVM) and a released target protein on immune cell migration in an organ-on-a-chip-based model. This setup allowed for the ranking of potential therapeutic antibodies.
Studying immune migration in the OrganoPlate®
The model used in this study features HUVEC (endothelium) in the top compartment, perfused with fluorescently labeled primary human immune cells, cultured under flow, and in direct contact with a collagen-I extracellular matrix gel. The collagen-I was enriched with primary macrophages or with the isolated target protein. Immune cell migration was quantified by fluorescent imaging.
A. The OrganoPlate 3-lane 64 platform with zoom-in on individual tissue chip. B, C. Representation of endothelial vessel, perfused with fluorescently labeled immune cells, aligning next to an extracellular matrix lane, comprising of embedded PVMs or target protein. Chip design allows for free migration of cells between lanes. Image Credit: Image courtesy of W. Strijker et al., in partnership with ELRIG (UK) Ltd.
PVMs create a suppressive environment
The addition of perivascular macrophages (PVMs) has been shown to have an inhibitory effect on immune cell migration, in contrast to pro-inflammatory M1 macrophages that increased the number of migrated immune cells.
Image Credit: Image courtesy of W. Strijker et al., in partnership with ELRIG (UK) Ltd.
Target-mediated immune migration
Increased concentration of target protein deposited in the extracellular matrix leads to reduced T cell migration. Effects are more profound with stimulated T cells. Cultures were pre-cultured with TNFα.
Image Credit: Image courtesy of W. Strijker et al., in partnership with ELRIG (UK) Ltd.
Antibody treatment
Novel therapeutic antibodies effects were assessed after target protein addition. Ab3 showed an increased migration of T cells.
Image Credit: Image courtesy of W. Strijker et al., in partnership with ELRIG (UK) Ltd.
PVM as a potential target
These findings highlight the potential of targeting PVMs and their released proteins. The study also shows the utility of this advanced in-vitro model for evaluating therapeutic antibodies in the context of an immunosuppressive microenvironment.
Reference
- Luuk de Haan, Suijker, J., et al. (2021). A Microfluidic 3D Endothelium-on-a-Chip Model to Study Transendothelial Migration of T Cells in Health and Disease. International Journal of Molecular Sciences, 22(15), pp.8234–8234. DOI: 10.3390/ijms22158234. https://pubmed.ncbi.nlm.nih.gov/34361000/.
About MIMETAS B.V.
MIMETAS B.V. develops organ-on-a-chip tissue models for evaluating drugs, chemicals and food components. Its unique microfluidic technology, designated OrganoPlates®, enables testing of compounds in high-throughput on miniaturized organ models. These models show better predictivity as compared to laboratory animals and conventional cell culture models.
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Last Updated: Nov 25, 2025