piggyBac system to co-express NKG2D CAR and IL-15 to augment the in vivo persistence and anti-AML activity of human peripheral blood NK cells

• DOI: 10.1016/j.omtm.2021.10.014
• Publication Date: 2021-11-04T03:39:49Z
• Authors: Zhicheng Du; Yu Yang Ng; Shijun Zha; Shu Wang
• Keywords: Augment; NKG2D; Persistence (discontinuity)

Promising progress has been made in adoptive transfer of allogeneic natural killer (NK) cells to treat relapsed or refractory acute myeloid leukemia (AML). In this regard, chimeric antigen receptor (CAR)-modification NK is considered as a compelling approach augment the specificity and cytotoxicity against AML. Using non-viral piggyBac transposon technology human peripheral blood-derived primary cells, we generated CAR-NK target NKG2D ligands demonstrated their vitro activity lysing cancer expressing vivo efficacy inhibiting tumor growth xenograft KG-1 AML model. We further co-expressing transgenes for CAR interleukin-15 (IL-15). The ectopic expression IL-15 improved persistence leading enhanced control significant prolongation mouse survival Collectively, our findings demonstrate an important means improve antileukemic cells. Our study illustrates feasibility using platform efficient cost-effective way cell manufacturing.