Previously, we have confirmed that SIRP α- Fc fusion protein IMM01 targeting SIRP α and CD24 monoclonal antibody IMM47 targeting CD24 can respectively block CD47/SIRP α and CD24/Siglec-10 signaling pathway, revealed strong anti-tumor activity. In this study, we confirmed that IMM01 has strong binding activity against various tumor cells, including Raji, Daudi, SU-DHL-10, Jurkat, HL-60, MV-4-11, Reh, HCC827, NCI-H1299, NCI-H2975, A549, BT474, SK-BR-3, SK-OV-3, Hela, AGS, and HT-29, limited binding activities to human T, B, NK, and monocyte cells. Importantly, there is no binding activity to red blood cells. The in vitro experiments revealed that the combination of IMM01 and IMM47 strongly blocks the interaction between CD47/SIRP and CD24/Seglec-10 and significantly enhances the phagocytic effect of macrophages on leukemia cells in vitro. The ADCC effect of IMM01 combined with IMM47 on leukemia cells of AML patients and normal human cells was measured. The results showed that IMM01 combined with IMM47 showed a strong ADCC effect on leukemia cells of AML patients in vitro, but no ADCC effect on normal human granulocytes and CD3+T cells. The HL-60 tumor cell xenotransplantation SCID mouse model in vivo pharmacological results showed that the combined treatment effect of IMM47 and IMM01 was significantly better than any single drug. Compared with the vehicle control group, the control CD47 monoclonal antibody, IMM01 monotherapy, IMM47 monotherapy, and IMM01 combined with IMM47 groups all significantly inhibited tumor growth (p<0.001). Compared with the CD47 control group, both the IMM47 monotherapy group and the IMM01 combined with IMM47 group significantly inhibited tumor growth (p<0.05). The combination of IMM01 and IMM47 produced excellent synergistic anti-tumor effects in this HL-60 xenotransplantation model. These results provide strong experimental support and solid theoretical foundation for the combination of IMM01 and IMM47 in the treatment of AML.

Jifeng Yu has completed his M.D. from Henan Medical University, China. He is a distinguished professor and chief physician in the department of Hematology at the First Affiliated Hospital of Zhengzhou University, Henan, China. He has over 100 research papers and two books that have been cited over 600 times, and his publication h-index is 11. He has been serving as an editorial board member of several reputed journals.