Effectiveness of Anti-CD47 antibody and Ara-C combination targeting therapy NOD/SCID mouse of myeloid leukemia

Objective To study the prognostic significance of CD47 in a NOD/SCID mouse model of acute myeloid leukemia(AML) and the best strategy for targeted therapy for this disease.Methods CD34+CD38-leukemia stem cells(LSCs) were separated and transplanted into NOD/SCID mice to establish a mouse model of acute monocytic leukemia(AMoL).Anti-human CD47 antibody,alone or combined with cytosine arabinoside(Ara-C),was used to treat the mice with AMoL for 7-14 days,and therapeutic efficacy was assessed.LSCs were cultured together with mouse macrophages in culture medium containing anti-CD47 or anti-CD45 monoclonal antibody for 2 hours,to observe the phagocytic ability of macrophages to LSCs.Results CD34+CD38-LSCs existed among THP-1 cells,with a content of about(0.12±0.06)%,and a mouse model of AML was successfully established after the purified CD34+CD38-LSCs(97.0%±1.7%) were transplanted into NOD/SCID mice.The in vivo experiment showed that mice with AMoL had the most significant decrease in CD33+CD45+ leukemia cells in peripheral blood and bone marrow and survived the longest after being treated with Ara-C(7 days) plus anti-CD47 monoclonal antibody(14 days)(P0.01).After 2 hours of in vitro culture,the phagocytic index in the culture medium containing anti-CD47 monoclonal antibody was significantly higher than in the culture medium containing anti-CD45 monoclonal antibody(76.9%±12.2% vs 7.60%±2.4%;P0.05).Conclusions High expression of CD47 is an adverse prognostic factor in AML.Combination therapy with anti-CD47 monoclonal antibody and Ara-C can effectively eliminate leukemia cells and LSCs,demonstrating great clinical significance in curing AML.