Identify the Goldilocks CAR: Cell avidity as a parameter for optimal CAR-antigen combinations
This study aimed to identify CAR T cells that bind high antigen-expressing targets but not low antigen-expressing cells.
Researchers validated low functioning and high functioning CAR T cells based on functional assays and used non-transduced T cells as a negative control (NC). T cell avidities were tested on adherent cells with low antigen expression, high antigen expression, or no antigen expression.
The cell avidity data correlated with a corresponding in vitro cell killing assay, showing antigen-dependent binding strengths and cell killing, respectively (Figure 1). The cell-killing results also demonstrated significantly higher toxicity induced by high functioning CAR T cells on low antigen-expressing healthy-like cells (Figure 2).
The z-Movi® can distinguish between T cell specificities to improve CAR T cell therapy. Cell avidity is a reliable readout for identifying optimal CARs that can minimize on-target/off-tumor activity by CAR T cells.