Student Institute of Zoology, Chinese Academy of Sciences (CAS), Beijing, China (People's Republic)
Abstract: The lack of persistence and short-term efficacy presents a major challenge for CAR-NK cell therapy. Here, we addressed this issue by developing pluripotent stem cell-derived NK progenitor (iNKP) cell therapy. Engineered to express CXCR4 and chimeric antigen receptors (CAR), the iNKP cells efficiently migrated to the bone marrow and generated CAR-iNK cells persisting in peripheral blood (PB) for over 80 days. Notably, CAR-iNKP cell therapy durably protected animals from tumour occurrence. Furthermore, infusion of CAR-iNKP cells following conventional chemotherapy eradicated minimal residual disease (MRD), leading to long-term complete remission. Our findings present a novel strategy to overcome the limitations of traditional CAR-NK cell therapy and offer a potential breakthrough in immunotherapy for tumour prevention and MRD elimination.