Abstract 4930: Cell Avidity: The Next-Gen cell binding assay to understand therapeutic mechanism of action through quantifying cell-cell and cell-protein interaction strength

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 the biophysical cell-cell interactions that drive functional processes. Methods: Cell avidity, the integrated strength of multivalent interactions between an effector cell and its target, can help elucidate the mechanism of action for therapeutic candidates. Our Cell Avidity platform challenges these interacting pairs using contactless force and quantifies the strength of binding between effector and target cells to distinguish productive from unproductive cell binding in a physiological context. This biophysical metric provides a unique view into cell binding characteristics to interrogate binding potency, selectivity, sensitivity, and kinetics. Results: Here, we review recent publications highlighting how researchers have used Cell Avidity to: • Fine-tune the affinity/cell avidity of CAR-T cells to mitigate on-target off-tumor toxicity in renal cell carcinoma. • Assess the impact of Venetoclax treatment on NK cells, finding improvements to cytoskeleton remodeling and lytic granule polarization, which contributed to a more efficient IS, enhancing NK cell-mediated killing of AML cells. • Format-tune bispecific T cell engagers to enhance efficacy against renal cell carcinoma • Validate binding mechanism of tandem CAR-T cells to overcome tumor heterogeneity • Engineer CAR-T cells secreting a T-cell engaging molecule to overcome a challenging tumor microenvironment in pancreatic adenocarcinoma. • Elucidate mechanism of action of tandem CAR-T targeting heterogenous solid tumors • Phenotype the tumor-primed NK cells for cell binding and function. Conclusions: 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, selectivity, sensitivity, and kinetics, offering key insights into the mechanism of action for cell therapies. Citation Format: Keith Bailey, Riley Pihl, Michael SAVAGE, Trey Simpson. Cell Avidity: The Next-Gen cell binding assay to understand therapeutic mechanism of action through quantifying cell-cell and cell-protein interaction strength [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2026; Part 1 (Regular Abstracts); 2026 Apr 17-22; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2026;86(7 Suppl):Abstract nr 4930.