Why T-cell avidity?
As shown on the figure at the left, cells can establish multiple interactions, for example between TCRs and pMHCs or various co-stimulatory molecules and co-receptors. Assessing the overall strength of all of these simultaneous interactions provides information about avidity which has been shown to correlate with the outcomes of cell-cell interactions. This information can be essential for immuno-oncology and of unprecedented value for future immune therapies, as the ability of T cells to recognize and encounter cancer cells is often dictated by their avidity.
So far, researchers have mostly been using surface plasmon resonance (SPR) to assess affinity. However recent studies have shown that affinity is a poor predictor of T-cell activation or functionality and cannot discriminate functional potency (Leah V. Sibener et al., 2018. Cell). On the other hand, techniques for avidity readouts, such as micropipette adhesion assay is technically challenging to use and provides low throughput. By contrast, the tetramer staining is a high-throughput fluorescence technique. However, recent findings have shown fluorescence determined by tetramer staining lead to false negative readouts of T-cell functionality (Zhang et al., 2016. Science Translational Medicine). Also, the established readouts are based on bulk populations, offering only averaged functionality readouts of the mixed population of T-cells.
Here, we present z-Movi™: a high throughput single-cell resolution, label-free, lab-on-a-chip technology that enables reliable high throughput measurements of T-cell avidity.