[ICI 2017] Immune Checkpoint Inhibitor Profiling and Biomarker Identification Using Human Primary Cell BioMAP Oncology Systems

[ICI 2017] Immune Checkpoint Inhibitor Profiling and Biomarker Identification Using Human Primary Cell BioMAP Oncology Systems
Version:
20730

File Name/Number:
2017 ICI

Year:
2017

With recent advances in cancer immunotherapies, the ability to evaluate candidate compounds in complex biological networks is becoming increasingly important. BioMAP Oncology systems consist of physiologically-relevant co-cultures of human primary fibroblasts or endothelial cells, immune cells, and cancer cell lines to model inflamed stromal or vascular host-tumor  microenvironments (TME). These are used to statistically evaluate the impact of agents on  protein biomarkers, based on a historical vehicle control significance envelope. Here, we investigated a panel of anti-cancer drugs with diverse mechanisms-of-action (MoA), including immunotherapies, kinase inhibitors, and microtubule stabilizers, in the BioMAP colorectal cancer panel (CRC) as well as in the BioMAP Diversity PLUS™ panel, which models a broad scope of non-cancer biology. Biomarker endpoints reflect selective impact on TME versus non-TME related responses.

Small molecule kinase inhibitors and microtubule stabilizers were active in both Diversity PLUS and CRC oncology systems consistent with their broad target/MoA impacting diverse cell types. In the Diversity PLUS panel, microtubule stabilizers and EGFR inhibitors decreased several inflammatory, immune, and tissue remodeling related biomarkers. In the CRC systems, these agents increased cytokine production consistent with a restored immune function effect. Similarly, anti-checkpoint receptor antibodies robustly increased cytokine levels in the CRC systems but in marked contrast, were inactive in the Diversity PLUS panel. This demonstrates that the immune restoring impact of these immunotherapeutics is restricted to the TME and these effects are not evident in the periphery. BioMAP quantitative phenotypic evaluation of compounds can be used to drive effective therapeutic strategies warranting further clinical evaluation.