Novel, Improved Cell-Based Assays to Enable Immunotherapy Drug Development for Checkpoint Receptors

摘要

Regulation of immune responses is tightly controlled through a balance of co-stimulatory and inhibitory checkpoint receptors, often exploited by many cancers. Therefore, therapeutics that block inhibitory receptors or activate immuno-stimulatory checkpoint receptors have proved to be powerful agents to restore anti-tumor immune responses. However, developing drugs targeting these checkpoint proteins has proved to be quite challenging as cell-based assays used to screen for functional drugs are often difficult to create, involve the use of human primary cells, and have long, complicated protocols. Here, we present data for several new PathHunter? Checkpoint assays that target clinically relevant co-inhibitory and costimulatory checkpoint receptors using the industry-validated Enzyme Fragment Complementation (EFC) technology. The PathHunter assays measure receptor activation and signaling for co-stimulatory receptors and co-inhibitory receptors. These assays facilitate the development of relevant therapeutics, enabling rapid and sensitive screening of biologies and small molecules. Furthermore, the robustness and reproducibility of these assays lend themselves well to use in lead optimization, relative potency, and QC lot release testing of immunotherapy drugs. These Mechanism of Action-based, biologically-relevant, cell-based assays do not require human primary cells and have an easy-to-use protocol, providing a highly sensitive response in less than 5 hours for the PD-1 Signaling assay. Here, we present data for assays targeting a number of clinically important immunotherapy targets, including PD-1 (with PD-L1 and PD-L2), ICOS, CD28, BTLA, and OX40.