OpenTox Virtual Conference 2023

High-throughput 3D spheroid co-culturing platform for investigation of tissue interactions and  combined efficacy/safety testing

We developed a high-throughput, 384-well-format platform for co-culturing two or more 3D spheroid models side-by-side, which is compatible with vast majority of laboratory devices and bioassays. As a proof of concept, we performed a combined assessment of anti-tumor efficacy and liver safety of bispecific antibodies. We employed 3D spheroids composed of primary human hepatocytes and Kupffer cells as liver model. The solid tumor model was aggerated from a human cancer cell line (HCT116-GFP) and primary cancer associated fibroblasts, mimicking the tumor microenvironment. We treated 3D spheroid models with runimotamab (HER2xCD3 bispecific antibody) in the presence of peripheral blood mononuclear cells (PBMCs). The treatment with runimotamab resulted in a significant decrease of fluorescence and size of tumor spheroids. At the same time, we observed an induced secretion of cytokines with a peak of expression of IL-2, TNFα after 24h and INFy, IL-6 and IL-17A after 48h. Cytokine release was coupled with elevated levels of clinically relevant liver damage biomarkers ALT and AST with peak at 72h timepoint.