Preferred Label : Anti-PD-1/CD47 Infusion Protein HX009;
NCIt synonyms : Anti-PD1/CD47 Bi-specific Antibody Fusion Protein HX009;
NCIt definition : A bispecific antibody fusion protein directed against the human negative immunoregulatory
checkpoint receptors programmed cell death protein 1 (PD-1; PDCD1; CD279) and the
human cell surface antigen CD47, with potential immunostimulating, phagocytosis-inducing
and antineoplastic activities. Upon administration of anti-PD-1/CD47 infusion protein
HX009, the agent simultaneously and selectively targets and binds to PD-1 expressed
on T-lymphocytes and CD47 on tumor cells. The CD47 binding by HX009 blocks the interaction
of CD47 with signal regulatory protein alpha (SIRPalpha), an inhibitory protein expressed
on macrophages and dendritic cells (DCs), which prevents CD47/SIRPalpha-mediated signaling
and abrogates the CD47/SIRPalpha-mediated inhibition of phagocytosis. This induces
pro-phagocytic signaling mediated by the binding of calreticulin (CRT), which is specifically
expressed on the surface of tumor cells, to low-density lipoprotein (LDL) receptor-related
protein (LRP), expressed on macrophages, which results in macrophage activation and
the specific phagocytosis of the CD47-expressing tumor cells. The binding of HX009
to PD-1 blocks the interaction between PD-1 and its ligands, PD-1 ligand 1 (PD-L1)
and PD-1 ligand 2 (PD-L2). This prevents the activation of PD-1 and its downstream
signaling pathways. This may restore effector T-cell functions and may further activate
cytotoxic T-lymphocyte (CTL)-mediated tumor cell killing. CD47, also called integrin-associated
protein (IAP), is a tumor-associated antigen (TAA), widely expressed on normal, healthy
cells, such as red blood cells and platelets, and overexpressed on the surface of
a variety of cancer cells. Expression of CD47, and its interaction with SIRPalpha,
leads to the inhibition of macrophage activation and protects cancer cells from phagocytosis,
which allows cancer cells to proliferate. By co-targeting CD47 and PD-1, HX009 has
the potential to overcome the limitations of existing CD47-targeted therapies by possibly
avoiding the side effects caused by binding to CD47 on healthy hematopoietic stem
cells (HSCs), which causes unwanted macrophage-mediated phagocytosis. PD-1, an inhibitory
receptor belonging to the immunoglobulin superfamily (IgSF), is expressed on activated
T-lymphocytes; it functions as an immune checkpoint that negatively regulates T-cell
activation and effector function when activated by its ligands, and plays an important
role in tumor evasion from host immunity.;
Molecule name : HX 009; HX-009;
NCI Metathesaurus CUI : CL972917;
Origin ID : C168600;
UMLS CUI : C5238973;
- Semantic type(s)
- concept_is_in_subset