P02.16 Cell avidity: the next-gen binding assay to advance immune-based therapeutic development

Background 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 contribution of CD58:CD2 in CAR mediated cell avidity and how replacing that with synthetic PD-1:CD2 interactions reduces fratricide while maintaining potencyFormat-tune bispecific T cell engagers to enhance efficacy against renal cell carcinomaValidate glyco-bridge binding in the context of CAR-T cells to overcome immunosuppressive tumor microenvironmentEngineer 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 tumorsPhenotype tumor-primed NK cells for cell binding and functionConclusions 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 essential information revealing potency, selectivity, sensitivity, and kinetics, offering key biophysical insights into the mechanism of action for immune-based therapies.