The ADAM17 Inhibition in Cord Blood Stem Cell Derived CD16 + NK Cells Enhanced Cytotoxicity against Acute Lymphoblastic Leukemia Cells

Abstract

Abstract Background: Fortunately, ample efforts are attempting to find the best strategy to improve the NK cell anti-leukemia capacity in the treatment of different types of cancers. Despite the favorable ADCC capacity of functional CD16+ NK cells for immunotherapy, when NK cells face leukemia cells, CD16 receptor is cleaved during the process mediated by matrix metalloproteinases (MMPs) ADAM17. The reduced CD16 expression on NK cells weakens their cytotoxicity against leukemia cells. As well, the expression of CD47 receptor is higher in acute lymphoblastic leukemia (ALL) compared to normal cells and is correlated with poor prognosis. Results:In the present study, ADAM17 was inhibited in cord blood derived CD16+ NK cells and then the activity against ALL cell lines was evaluated following blockage with anti-CD47 antibody. Since the CD16 expression reduces on co-cultured NK cells with ALL cell lines, ADAM17 inhibitor increases CD16+ NK cells cytotoxicity with high expression of CD107-a as well as INF-γ production, which consequently raise the apoptosis effects in cancer cell lines. Conclusions: Therefore, the inhibition of ADAM17 is necessary for the CD16+ NK cells activity against cancer cells.