Abstract 89: Comprehensive cell based bioassay approaches for characterization, and clinical development of therapeutic agonistic antibodies for cancer immunotherapy and autoimmune diseases

Abstract Agonistic antibodies are emerging as promising therapeutics for targeting immune checkpoints, particularly those within the TNF Receptor Superfamily, as they play a crucial role in regulating immune cell function, especially in the context of cancer treatment. In addition, there is also a growing focus on the potential of agonistic antibodies to selectively activate co-inhibitory checkpoint receptors. This offers a promising avenue for suppressing inflammation in autoimmune diseases and restoring tolerance in graft-vs-host disease (GvHD) while avoiding the complications of global immunosuppression. While a substantial number of clinical trials are currently underway for oncology and autoimmune indications, there is a notable scarcity of commercially available assays to support the clinical development of this class of therapeutics, impacting their time-to-clinic. Existing assays frequently fail to accurately assess the agonistic activity of antibodies as they are unable to replicate the necessary physiologically relevant conditions. In this context, we present several case studies that highlight the pivotal role of cell-based bioassay approaches developed by Eurofins DiscoverX in driving the characterization and clinical development of agonistic antibody therapeutics targeting various checkpoint receptors. Additionally, we discuss our data demonstrating the indispensable role of FcyR-mediated antibody clustering in establishing the otherwise elusive agonistic activity of antibodies. Citation Format: Venkatesh Chari, Jennifer Lin-Jones, Luhan Yang, Jane E. Lamerdin, Gaurav Agrawal. Comprehensive cell based bioassay approaches for characterization, and clinical development of therapeutic agonistic antibodies for cancer immunotherapy and autoimmune diseases abstract. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts) ; 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84 (6Suppl): Abstract nr 89.