Abstract B048: Next Generation Binding: Measuring Cell Avidity to Fully Characterize Cell-Cell Interactions and Understand Mechanism of Action for Cellular Therapies

Abstract While conventional assays such as affinity, cytokine secretion, and cytotoxicity provide valuable data at a molecular level, this information is insufficient to fully characterize and select the best cellular therapies. There is still a lack of understanding about cell-cell interactions that drive functional processes. Cell Avidity, the collective strength of interactions between an effector and its target, can help elucidate the mechanism of action for therapeutic candidates. Our highly flexible Cell Avidity platform, the z-Movi Cell Avidity Analyzer, combines fluorescence microscopy with acoustic force to distinguish cell binding in a physiological context. This provides a comprehensive view of cell binding characteristics to interrogate potency, safety, sensitivity, and binding kinetics. Cell avidity has been used to: 1) Engineer CAR-T cells secreting a T-cell engaging molecule to overcome a challenging tumor microenvironment in pancreatic adenocarcinoma. 2) Reveal critical neutrophil-tumor cell interactions in the tumor microenvironment. 3) Identify essential proteins involved in B-cell lymphoma binding to stromal cells in the tumor microenvironment. 4) Fine-tune the affinity/cell avidity of CAR-T cells to mitigate on-target off-tumor toxicity in renal cell carcinoma. 5) Format-tune in vivo-launched bispecific T cell engagers to enhance efficacy against renal cell carcinoma. 6) Characterize the mechanism of action to assess the function and efficacy of NK-cell cytotoxicity. Cell Avidity is an emerging biomarker that directly quantifies the strength of the physical interactions between target and effector cells. We developed a Cell Avidity platform that enables characterization and screening of molecular binders and cellular products, including antibodies, small molecules, and cell therapies. Citation Format: Song-My Hoang. Next Generation Binding: Measuring Cell Avidity to Fully Characterize Cell-Cell Interactions and Understand Mechanism of Action for Cellular Therapies [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Tumor Immunology and Immunotherapy; 2024 Oct 18-21; Boston, MA. Philadelphia (PA): AACR; Cancer Immunol Res 2024;12(10 Suppl):Abstract nr B048.