Cord blood stem cell derived CD16⁺ NK cells eradicated acute lymphoblastic leukemia cells using with anti-CD47 antibody

Acute lymphoblastic leukemia (ALL) is an aggressive cancer in children and adults which possess higher CD47 expression than normal cells. ALL chemotherapy has a lot of side effects and in most cases is ineffective. However arrival of Natural killer (NK) cell immunotherapy raised hopes for successful treatment of cancers, tailoring NK cells to meet clinical requirements is still under investigation. Of note, CD16⁺ (FCγIIIa) NK cells eliminate tumor cells with antibody dependent cell cytotoxicity (ADCC) mechanism. Therefore, we evaluated ADCC effect of cord blood stem cell derived CD16⁺ NK cells with using anti CD47 blocking antibody. CD16⁺ NK cells generated efficiently from CD34 positive cord blood cells in vitro using IL-2, IL-15 and IL-21 cytokines, although it was not dose dependent. CD16⁺ cells derived from CD34⁺ cells in day 14 of culture efficiently increased apoptosis in ALL cells, produced INFγ and increased CD107-a expression when used anti CD47 antibody (increased around 30–40%). Interestingly, CD16⁺ NK cell cytotoxicity slightly increased in combination with macrophages against ALL cells (around 10%). Taken together, our findings induced this hope that cord blood stem cell derived CD16⁺ NK cells exploit antitumor immune response in cancer therapy with using anti-CD47 antibody.