Anti-Relapse effects of donor natural killer cells and IL-2 gene modification on allogeneic hematopoietic stem cell transplantation in acute leukemia

Abstract

BACKGROUND: Patients with acute leukemia (AL) refractory to induction or reinduction chemotherapy show poor prognoses if they do not undergo allogeneic hematopoietic stem-cell transplantation (AHSCT). The present study aims to investigate whether donor natural killer (NK) cells and interleukin-2 (IL-2) gene modification exert anti-relapse effects on AHSCT after establishing a mouse model of AL. METHODS: C57BL/6 (H-2b) mice were selected as donor mice to obtain NK cells and hematopoietic stem cells, while BALB/c (H-2d) mice were selected as the recipient mice for AHSCT. The AHSCT-treated mice were then injected with the donor NK cells, recombinant adenovirus expressing IL-2 (AdIL-2), or the NK cells infected by AdIL-2. Flow cytometry was performed to detect the cell transplantation rate, immune cell number, and cell immunogenicity. Enzyme-linked immunosorbent assay (ELISA) was employed to quantify the secretion of IL-2 in spleen cells, and the level of peripheral blood factors, including interferon-γ (IFN-γ), tumor necrosis factor-α (TNF-α), IL-35, transforming growth factor β (TGF-β), and IL-10. RESULTS: In our experiments, promotional effects of NK cells and AdIL-2 were found on cell transplantation rate, immune reconstitution ability, cell immunogenicity, IL-2 secretion, as well as increased peripheral blood factor levels in the recipient mice treated with AHSCT, with improved pathological changes observed. Moreover, the aforementioned changes were further promoted in the AHSCT-treated recipient mice injected with the AdIL-2-infected NK cells. CONCLUSIONS: These results uncover that the donor NK cells and IL-2 gene modification could inhibit the relapse of AL mice underwent AHSCT, hereby providing a new target for leukemia treatment.