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Analysis of α-PD-1, α-PD-L1 and α-CTLA-4 Immune Checkpoint Antibodies in Human Primary Cell BioMAP® Oncology Systems


The emergence of novel drugs including targeted biologics show compelling efficacy in oncology. The ability to test new agents, alone or in combination, in predictive human disease models supports the identification, optimization and application of new therapeutic strategies. Our goal is to develop more robust and physiologically relevant in vitro models of the host-tumor microenvironment. In that regard, stimulated co-cultures of human primary fibroblasts or endothelial cells with a colorectal cancer (CRC) cell line (HT29) and immune cells were used to develop CRC microenvironment disease models. Using these models, we characterized the expression of immune checkpoint proteins and activity of the antibodies targeting these proteins. Using flow cytometric analysis, we evaluated the protein expression of PD-1, CTLA-4, PD-L1 and PD-L2 on specific cell populations in these host-tumor models. Further, we demonstrated differential effects on expression of immune checkpoint biomarkers and immune and angiogenesis related activities consistent with impact of tumor-mediated immune suppression. α-PD-1 and α -PD-L1 antibodies increased immune-related activities, as measured by the modulations of cytokines and immune-related protein biomarkers. In contrast, α -CTLA-4 antibody had only modest immunomodulatory effects, consistent both with the expression level of CTLA-4 in our BioMAP Systems as well as reported clinical results from patients.
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