The inhibition of ADAM17 in cord blood stem cell-derived CD16+ NK cells to enhance their cytotoxicity against acute lymphoblastic leukemia cells

Fortunately, ample efforts are being made to find the best strategy to improve the anti-leukemia capacity of NK cells for treating different types of cancer. Despite the favorable ADCC capacity of functional CD16 + NK cells for immunotherapy, when NK cells face leukemia cells, the CD16 receptor is cleaved during the process mediated by a disintegrin and metalloproteinase-17(ADAM17). Reduced CD16 expression on NK cells weakens their cytotoxicity against leukemia cells. In addition, the expression of the CD47 receptor is high in acute lymphoblastic leukemia (ALL) compared to normal cells and can be correlated with poor prognosis. In the present study, ADAM17 was inhibited in cord blood-derived CD16 + NK cells, and their activity against ALL cell lines was evaluated following blockage with anti-CD47 antibody. As the results showed, the CD16 expression was reduced in the NK cells co-cultured with ALL cell lines. However, the ADAM17 inhibition increased the CD16 expression on the NK cells. This enhanced the cytotoxicity of those cells as well as cytokine production was evaluated by measuring expression of CD107-a expression, and IFN-γ production. Moreover, the presence of the ADAM17 inhibitor increased the apoptosis effect of the generated NK cells in response to ALL cells. Therefore, the inhibition of ADAM17 is useful for the activity of CD16 + NK cells against cancer cells.