Preferred Label : Safimestomig;
NCIt synonyms : CD47 x PD-L1 Bispecific Antibody 6MW3211; Anti-CD47/PD-L1 Bispecific Antibody 6MW3211; Anti-CD47/Anti-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, safimestomig targets and binds
to both CD47 and PD-L1 expressed on tumor cells. The CD47 binding by safimestomig
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 safimestomig 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, safimestomig 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).;
UNII : LFQ9PP64F2;
CAS number : 2911590-72-0;
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
