Preferred Label : Anti-CD47/Anti-PD-L1 Bispecific Antibody 6MW3211;
NCIt synonyms : CD47 x PD-L1 Bispecific Antibody 6MW3211; Anti-CD47/PD-L1 Bispecific Antibody 6MW3211;
NCIt definition : A humanized bispecific antibody targeting both the human cell surface antigen CD47
and the immunosuppressive ligand human programmed cell death-1 ligand 1 (PD-L1; cluster
of differentiation 274; CD274), with potential immunostimulating, phagocytosis-inducing
and antineoplastic activities. Upon administration, anti-CD47/anti-PD-L1 bispecific
antibody 6MW3211 targets and binds to both CD47 and PD-L1 expressed on tumor cells.
The CD47 binding by 6MW3211 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), specifically expressed on the surface of tumor cells,
to low-density lipoprotein (LDL) receptor-related protein (LRP), expressed on macrophages,
and results in macrophage activation and the specific phagocytosis of CD47-expressing
tumor cells. The binding of 6MW3211 to PD-L1 blocks its binding to and activation
of its receptor, programmed cell death 1 (PD-1; cluster of differentiation 279; CD279).
This reverses T-cell inactivation caused by PD-1/PD-L1 signaling and enhances the
cytotoxic T-lymphocyte (CTL)-mediated anti-tumor immune response against PD-L1-expressing
tumor cells. 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, which protects cancer cells from phagocytosis and allows proliferation
of cancer cells. PD-L1 is overexpressed by many human cancer cell types. PD-L1 binding
to PD-1, a transmembrane protein belonging to the immunoglobulin superfamily (IgSF)
that is expressed on activated T-cells, suppresses the immune system and results in
immune evasion. By co-targeting CD47 and PD-L1, 6MW3211 may more selectively bind
to tumor cells expressing both CD47 and PD-L1, reducing the side effects caused by
the blockade of CD47 expressed on healthy hematopoietic stem cells (HSCs).;
Molecule name : 6MW3211;
NCI Metathesaurus CUI : CL1772556;
Origin ID : C184379;
UMLS CUI : C5666926;
Semantic type(s)
- chemical_or_drug_has_mechanism_of_action
- concept_is_in_subset
- has_target
