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

Analysis of α-PD-1, α-PD-L1 and α-CTLA-4 Immune Checkpoint Antibodies
in Human Primary Cell BioMAP Oncology Systems
Year:
2015

1. Our goal is to develop more robust and physiologically relevant in vitro models of the host-tumor microenvironment
 
• Co-cultures of human primary fibroblasts or endothelial cells with a colorectal cancer (CRC) cell line
(HT29) and immune cells

2. Here, we characterize the expression of immune checkpoint proteins and demonstrate activity of immune
checkpoint antibodies in the CRC microenvironment models
 
3. 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
 
4. Further, we demonstrate differential effects on expression of immune checkpoint markers and immune and
angiogenesis-related activities consistent with impact of tumor-mediated immune suppression
 
• a-PD1 and a-PD-L1 increased immune-related activities, as measured by the modulations of cytokines and immune-related protein biomarkers
• In contrast, a-CTLA-4 had only modest immunomodulatory effects, consistent both with the expression of CTLA-4 in our BioMAP systems as well as reported clinical results from patients