CHEMOKINE RECEPTOR ENGINEERING OF NATURAL KILLER CELLS TO IMPROVE HOMING AND ANTI-TUMOUR EFFICACY

Abstract

Adoptive transfer of natural killer (NK) cells has been increasingly used to treat various kinds of cancer due to their intrinsic property to attack tumour cells without antigen sensitization. Tumours employ various strategies to escape surveillance from the immune system, including the down-regulation NK cells attracting chemokines. In light of this, we used mRNA electroporation to overexpress the chemokine receptors CXCR1 or CXCR4 on ex vivo expanded NK cells and demonstrated that the migration ability of NK cells could be restored towards CXCR1 ligand or CXCR4 ligand, respectively. The enhanced migration was also demonstrated in various in vivo tumour models. By further expressing a relevant chimeric antigen receptor (CAR) on top of NK cells overexpressing a chemokine receptor, their anti-tumour function was significantly improved. We believe that it would be beneficial to future treatments by incorporating this dual approach in NK cell therapy to enhance tumour clearance in patients.