Dual blockade of CD47 and CD24 signaling using a novel bispecific antibody fusion protein enhances macrophage immunotherapy

• DOI: 10.1016/j.omto.2023.100747
• Publication Date: 2023-11-04T17:28:14Z
• Authors: Yun Yang; He Wu; Yan Yang; Yan Kang; Runjia He; Bei Zhou; Huaizu Guo; Jing Zhang; Jianqin Li; Chunpo Ge; Tianyun Wang
• Keywords: CD47; Cancer Immunotherapy; CD24

CD47 and its receptor signal regulatory protein α (SIRPα) act as a dominant antiphagocytic, "don't eat me" signal. Recent studies reveal CD24 novel target for cancer immunotherapy by macrophages in ovarian breast cancer. However, whether simultaneous blockade of bispecific antibody may result potential synergy is still unclear. In the present study, we first time designed developed fusion protein, PPAB001 cotargeting CD24. Data demonstrate that CD47/SIRPα CD24/Siglec-10 signaling potently promoted macrophage phagocytosis tumor cells. Compared to single or targeting agents, was more effective inhibiting growth both mouse 4T-1 syngeneic human SK-OV-3 xenogeneic models. Mechanistically, found therapy markedly increased proportion tumor-infiltrating upregulated interleukin-6 necrosis factor-α levels were representative inflammatory cytokines. Notably, an ratio M1/M2 mice treated with suggested dual promote transition from M2 M1. Taken together, our data supported development immunotherapeutic treatment double-positive cancers.