Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 1 de 1
Filter
Add more filters










Database
Language
Publication year range
1.
Adv Sci (Weinh) ; 11(24): e2306388, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38477522

ABSTRACT

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.


Subject(s)
CD47 Antigen , Macrophages , Receptors, Immunologic , CD47 Antigen/immunology , CD47 Antigen/metabolism , Animals , Receptors, Immunologic/metabolism , Mice , Macrophages/immunology , Macrophages/drug effects , Macrophages/metabolism , Disease Models, Animal , Myocardial Infarction/immunology , Immune Checkpoint Inhibitors/pharmacology , Antigens, Differentiation/immunology , Phagocytosis/drug effects , Biomimetics/methods , Humans , Efferocytosis
SELECTION OF CITATIONS
SEARCH DETAIL