LAUSR

Immune checkpoint receptors play a critical role in maintaining immune homeostasis and are genetically and functionally associated with autoimmune disease, cancer and persistent viral infections. Blockade of immune checkpoints has emerged as a promising new approach to enhance anti-tumor immune responses. After initial successes with PD-1 and CTLA-4-targeted therapies, immunotherapy research has broadened to include additional immune checkpoint receptors targeted individually or in combination. A significant challenge in the development of biologics that target immune checkpoints is access to quantitative and reproducible functional bioassays. Existing methods rely on primary cells and measurement of complex functional endpoints. As an alternative to primary cell assays, we have developed a panel of cell-based reporter bioassays that can quantitatively determine the potencies of biologics targeting the immune checkpoints PD-1, CTLA-4, LAG-3, TIM-3, TIGIT, and BTLA, or bispecific antibody or antibody cocktails targeting two immune checkpoint receptors such as PD-1+TIGIT, PD-1+LAG-3, and PD-1+CTLA-4. These assays consist of engineered T effector cells that express luciferase reporters driven by specific response elements integrating signaling from the T cell receptor and immune checkpoint target(s), and engineered artificial antigen presenting cells. These mechanism of action-based bioassays demonstrate high specificity, sensitivity and reproducibility. Therefore they can serve as valuable tools for immunotherapy drug development. Citation Format: Jamison Grailer, Julia Gilden, Pete Stecha, Denise Garvin, Jim Hartnett, Frank Fan, Mei Cong, Zhi-Jie Jey Cheng. Quantitative cell-based bioassays to advance individual or combination immune checkpoint immunotherapy [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 2729.