Abstract 5672: Quantitative cell-based assays for characterization of antibodies targeting co-stimulatory immune checkpoint receptors

Abstract

Abstract The human immune system is regulated by a broad network of co-inhibitory and co-stimulatory receptors that control the type, scale, and duration of immune responses. These receptors are now recognized as promising immunotherapy targets for the treatment of many cancers and autoimmune diseases. Immunotherapies that block co-inhibitory receptors such as PD-1 and CTLA-4 are showing unprecedented efficacy in the treatment of some tumors, and have generated interest in the characterization of additional immunotherapy targets that may broaden the number of patients who can be helped by these drugs. Immunotherapy research programs are now exploring a wide range of both co-inhibitory (e.g. LAG-3, TIGIT, Tim-3) and co-stimulatory (e.g. GITR, 4-1BB, OX40) receptors, individually and in combination. Quantitative and reproducible functional bioassays are essential tools in the development of biologics for cancer immunotherapy. Most existing assays rely on primary cells and suffer from lengthy protocols and high day-to-day and donor-to-donor variability. These approaches are cumbersome, error-prone, and do not produce data of the quality required for drug development in a quality control environment. To address this, we have developed a suite of cell line-based reporter bioassays for co-stimulatory immune checkpoint targets including GITR, 4-1BB, OX40, and CD40. In these assays, stable cell lines express luciferase reporters driven by response elements under the precise control of intracellular signals mediated by each co-stimulatory receptor. These bioassays reflect mechanisms of action for drug candidates designed for each co-stimulatory receptor and demonstrate high specificity, sensitivity and reproducibility. Reporter-based bioassays can serve as powerful tools in immunotherapy drug development for antibody screening, potency testing and stability studies. Citation Format: Julia K. Gilden, Jun Wang, Michael Beck, Jamison Grailer, Jim Hartnett, Frank Fan, Mei Cong, Zhe-jie Jey Cheng. Quantitative cell-based assays for characterization of antibodies targeting co-stimulatory immune checkpoint receptors [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 5672. doi:10.1158/1538-7445.AM2017-5672