Background With the increasing complexity of cell therapy construct design, novel methodologies to accelerate screening and improve evaluation of lead candidates for clinical benefit are needed. Several methods are currently employed including receptor-ligand affinity measurements. However, affinity between T cell receptors (TCRs) and peptide-MHC complexes (pMHC) has shown to be a poor predictor of T cell functional capacity.
Methods We have developed the z-Movi Cell Avidity Analyzer to directly measure the overall binding strength, or cellular avidity, of effector to their target. Unlike affinity, cellular avidity is driven by the overall strength of dynamic surface interactions between effector cells and their targets; this novel biomarker integrates receptor density, the sum of individual affinities, and engagement of the multitude of co-receptors within the immunological synapse to characterize the interaction in a more biologically relevant context.
Results We will discuss how increased specific cellular avidity, i.e., TCRs with the strongest antigen binding and the lowest background binding, correlated with improved effector function in vitro and in vivo. Another application of measuring cell avidity explored the effect of changes to the glycosylation pattern on the cell surface of BMDC on T cell activation. Here, altered glycosylation patterns on BMDC increased avidity towards T cells leading to enhanced T cell function upon Ag recognition. These results demonstrated the benefits of understanding cell avidity to predict and select potent T cell candidates or bispecific antibodies.
Conclusions These results demonstrated the benefits of understanding cell avidity to predict and select potent T cell candidates or bispecific antibodies.
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