Chimeric antigen receptor (CAR) T-cell therapy has emerged as a promising approach for treating various forms of cancer. However, the mechanisms that govern CAR T-cell functionality and the associated side effects continue to be a subject of ongoing investigation. The establishment of the immunological synapse is crucial for activating signaling pathways, including those that are Ca2+-dependent. In this study, we demonstrated the functional significance of Kv1.3 channels within a CAR T-cell model. Our results underscore the colocalization of the Kv1.3 channel with the CAR and its redistribution into the synapse formed between the CAR and the target cell. Furthermore, the inhibition of lateral movement of Kv1.3 channels to the synapse between a CAR T-cell and a tumor cell annulled the cytotoxic capacity of CAR-T cells, likely by disrupting the Ca2+-response during immunological synapse formation. These results imply that ion channels could be a target in improving CAR T-cell therapy.
The findings of this study are published in the Journal of Immunology.
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