GENERATION OF CAR NK CELLS WITH A NON-VIRAL SYSTEM AND K562 ARTIFICIAL ANTIGEN PRESENTING CELLS

Abstract

CAR-NK cells are recently developed as an alternative treatment to CAR-T cells due to their targeting specificity to cancer cells, enriched intracellular activity with the alloreactive potential and innate anti-tumor functions. However, NK cells’ short lifespan without cytokine supports in vivo and the difficulties of genetic modifications to stably express CAR on NK cells have become the key obstacles for CAR-NK cells therapy to be applied in clinical settings. In this research, by using a non-viral piggyBac transposon technology and K562 artificial antigen presenting cells, we generated CAR-NK cells to target NKG2D ligands and demonstrated their in vitro activity in lysing cancer cells expressing the ligands and in vivo efficacy in inhibiting tumor growth in a xenograft KG-1 AML model. The ectopic expression of IL-15 could further improve the persistence of NKG2D CAR-NK cells with superior anti-tumor effects, suggesting their huge potential in the field of immunotherapy for cancer treatment.