传出细胞增多
CD47型
免疫系统
内吞作用
巨噬细胞
单克隆抗体
细胞生物学
癌症研究
抗体
细胞
生物
免疫学
免疫疗法
生物化学
体外
作者
Jiantou Gao,Zhiqing Pang,Qiaozi Wang,Yiwen Tan,Qiyu Li,Haipeng Tan,Jing Chen,Wusiman Yakufu,Zhengmin Wang,Hongbo Yang,Jinyan Zhang,Dili Sun,Xueyi Weng,Qibing Wang,Juying Qian,Yanan Song,Zheyong Huang,Junbo Ge
标识
DOI:10.1002/advs.202306388
摘要
CD47-SIRPα axis is an immunotherapeutic target in tumor therapy. However, current monoclonal antibody targeting CD47-SIRPα axis is associated with on-target off-tumor and antigen sink effects, which significantly limit its potential clinical application. Herein, a biomimetic nano-degrader is developed to inhibit CD47-SIRPα axis in a site-specific manner through SIRPα degradation, and its efficacy in acute myocardial infarction (AMI) is evaluated. The nano-degrader is constructed by hybridizing liposome with red blood cell (RBC) membrane (RLP), which mimics the CD47 density of senescent RBCs and possesses a natural high-affinity binding capability to SIRPα on macrophages without signaling capacity. RLP would bind with SIRPα and induce its lysosomal degradation through receptor-mediated endocytosis. To enhance its tissue specificity, Ly6G antibody conjugation (aRLP) is applied, enabling its attachment to neutrophils and accumulation within inflammatory sites. In the myocardial infarction model, aRLP accumulated in the infarcted myocardium blocks CD47-SIRPα axis and subsequently promoted the efferocytosis of apoptotic cardiomyocytes by macrophage, improved heart repair. This nano-degrader efficiently degraded SIRPα in lysosomes, providing a new strategy for immunotherapy with great clinical transformation potential.
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