Abstract A036: Cell Avidity – The Next-Gen cell binding to understand the mechanism of action through cell-cell and cell-protein interaction

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. Methods: 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. Results: Here, we review recent publications highlighting how researchers have used Cell Avidity to: •Format-tune in vivo-launched bispecific T cell engagers to enhance efficacy against renal cell carcinoma. •Venetoclax-treated NK cells to improve cytoskeleton remodeling and lytic granule polarization, contributed to a more efficient IS, enhancing NK cell-mediated killing of AML cells. •Engineer CAR-T cells secreting a T-cell engaging molecule to overcome a challenging tumor microenvironment in pancreatic adenocarcinoma. •Phenotype the tumor-primed NK cells for cell binding and function •Fine-tune the affinity/cell avidity of CAR-T cells to mitigate on-target off-tumor toxicity in renal cell carcinoma. Conclusions: 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 the characterization and screening of molecular binders and cellular products, including antibodies, small molecules, and cell therapies. Cell Avidity provides comprehensive information on potency, safety, sensitivity, and kinetics, offering key insights into the mechanism of action for cell therapies. Citation Format: Russell W Mellen, Justin Moser. Cell Avidity – The Next-Gen cell binding to understand the mechanism of action through cell-cell and cell-protein interaction [abstract]. In: Proceedings of the AACR IO Conference: Discovery and Innovation in Cancer Immunology: Revolutionizing Treatment through Immunotherapy; 2025 Feb 23-26; Los Angeles, CA. Philadelphia (PA): AACR; Cancer Immunol Res 2025;13(2 Suppl):Abstract nr A036.