Category: Biologics Discovery
The human immune system contains a complex network of immune checkpoint receptors that are promising as new immunotherapy targets for the treatment of cancers and autoimmune-mediated disorders. Immunotherapies designed to block co-inhibitory receptors (e.g., PD-1, CTLA-4) are showing unprecedented efficacy in the treatment of cancer. However, not all patients and tumor types respond to this approach. This has resulted in revised approach to immunotherapy research - to target additional co-inhibitory (e.g., LAG-3, TIM-3) and co-stimulatory (e.g. GITR, 4-1BB, OX40, CD40) receptors individually and in combination.
A major challenge in the development of biologics is access to quantitative and reproducible functional bioassays. Traditional methods rely on primary cells and measurement of complex functional endpoints. These assays are cumbersome, highly variable and fail to yield data of quality required for drug development in a quality-controlled environment. To address this need, we have developed a suite of cell-based functional bioassays to interrogate modulation of immune checkpoint receptors individually (e.g., PD-1, LAG-3, TIM-3, GITR, 4-1BB) and in combination (e.g., PD-1+CTLA-4, PD-1+LAG-3). These assays consist of stable cell lines that express luciferase reporters driven by response elements under the precise control of mechanistically relevant intracellular signals. Thus, the bioassays reflect mechanisms of action for the drug candidates designed for each immune checkpoint receptor and demonstrate high specificity, sensitivity and reproducibility. In summary, these reporter-based bioassays can serve as powerful tools in immunotherapy drug development for antibody screening, potency testing and stability studies.
Neal Cosby– Commercialization Manager, Promega Corporation, Sunnyvale, CA