Professor Leiden University, Zuid-Holland, Netherlands
An approach for drug (target) discovery and development is discussed using arrays of ECM-embedded cell clusters. The arrays are developed using automated image-guided injection of nanoliter droplets of cells into ECM scaffolds. We show how automated quantitative image analysis of ECM remodeling between clusters of fibroblasts can be used to identify anti-fibrotic drug candidates. The same approach is used for quantitative analysis of ECM remodeling capacity of cancer-associated fibroblasts and tumoroids, which we find to steer aspects of tumor angiogenesis that can be pharmaceutically targeted. Lastly, we show how arrays of ECM-embedded tumoroids can be harnessed to test engineered T cells for adoptive transfer protocols and to screen and optimize therapeutics for immune oncology. Thus, a medium throughput, reproducible, 3D co-culture setup combined with quantitative high content imaging tools is sufficiently versatile to identify and optimize drug candidates in oncology and fibrosis.