S910 a New Membrane‐bound Il‐21/4–1bbl‐expanded Nk Product Exhibits Activity Against Acute Myeloid Leukemia Activity in Vivo

Abstract

Background:Adoptive NK cells infusion is a promising immunotherapy for acute myeloid leukemia (AML) patients.Aims:The aim of this study was to explore that two weeks of clinical grade expansion could provide sufficient numbers and purity of NK cells for clinical application with an enhanced ant‐leukemia response in vitro.Methods:NK cells were expanded in the large‐scale expansion platform based on membrane‐bound interleukin‐21/4–1BBL K562 feeder cells (mbIL21/4‐1BBL). The phenotype as well as responsitveness of NKcells were evaluated before and post NK cells expansion. NCG mouse model were used to assess the in vivo persistence and in vivo anti‐leukemia effect of NK products. Finally, 20 minimal residual disease persistent or relapse (MRD+) AML were enrolled to evaluate the safety of adoptive expanded NK products infusion.Results:In this study, using the large‐scale expansion platform, we first demonstrated that 2 weeks of expansion could satisfy clinical use in number (∼4.1 × 109 NK cell) and purity (median 81%) from 2 × 107 peripheral blood mononuclear cells based on membrane‐bound interleukin‐21/4‐1BBL K562 feeder cells (mbIL21/4‐1BBL), with expansion folds of 1318 and 2876 at 2 and 3 weeks, respectively. The CD107α production as well as TNF‐α secretion capacity of NK products against AML cell lines, or primary AML blasts, were comparable between 2 weeks and 3 weeks expanded NK products, both of which were higher than those resting NK cells before expansion. The MbIL21/4‐1BBL expanded NK product xenografted into immunodeficient leukemia mice could be found in bone marrow, spleen, liver, lung and peripheral blood, persisting for at least 2 weeks and reducing the AML burden in vivo. NK cells infusions once, or three times every other days exhibited similar tumor control. Compared with the case‐paired 20 minimal residual disease persistent or relapse (MRD+) AML patients with regular consolidation therapy, 20 AML MRD+ patients who accepted the expanded NK treatment showed better leukemia‐free survival and overall survival.Summary/Conclusion:In conclusion, this study demonstrated that mbIL‐21/4‐1BBL expanded NK cells exhibited anti‐leukemia activity against AML in vitro and in a mouse model, and the infusion of expanded NK product was potentially efficacious for AML patient without adverse effects.