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

Abstract:

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) (P<0.01). 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%; P<0.05). 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.