Functional role of Kv1.3 localization in chimeric antigen receptor T cells.

Chimeric antigen receptor (CAR) T-cell therapy has proven to be a promising treatment for multiple types of cancer. Yet, the mechanisms regulating CAR T-cell function as well as the side effects remain an area of active research. The formation of the immunological synapse is essential for the activation of signaling pathways including the Ca2+-dependent one. Here we demonstrated the functional role of Kv1.3 channels in a CAR T-cell model. Our findings highlight the colocalization of Kv1.3 channel with CAR and its redistribution into the synapse between a CAR T and target cell. The biophysical properties of Kv1.3 channel are not vastly affected by the introduction of CAR in the cells. The blockage of this ion channel's lateral movement affects the killing potential of CAR T cells, likely via disruption of the Ca2+ response upon IS formation. Overall, these data suggest that the manipulation of the Kv1.3 channel may contribute to the improvement of CAR T-cell immunotherapy and provide new insights for future clinical strategies.